Inhibitor of vascular endothelial cell growth factor

1 . A soluble VEGF inhibitor in substantially pure form which specifically binds VEGF and inhibits cellular VEGF receptor activity.

2 . The soluble VEGF inhibitor according to claim 1 wherein the soluble VEGF receptor is selected from the group consisting of sVEGF-RI, sVEGF-RII, sVEGF-RTMI and sVEGF-RTMII.

3 . The soluble VEGF inhibitor of claim 2 corresponding to sVEGF-RI comprising the amino acid sequence:

Met Val Ser Tyr Trp Asp Thr Gly

(SEQ. ID. NO.:6)

Val Leu Leu Cys Ala Leu Leu Ser

Cys Leu Leu Leu Thr Gly Ser Ser

Ser Gly Ser Lys Leu Lys Asp Pro

Glu Leu Ser Leu Lys Gly Thr Gln

His Ile Met Gln Ala Gly Gln Thr

Leu His Leu Gln Cys Arg Gly Glu

Ala Ala His Lys Trp Ser Leu Pro

Glu Met Val Ser Lys Glu Ser Glu

Arg Leu Ser Ile Thr Lys Ser Ala

Cys Gly Arg Asn Gly Lys Gln Phe

Cys Ser Thr Leu Thr Leu Asn Thr

Ala Gln Ala Asn His Thr Gly Phe

Tyr Ser Cys Lys Tyr Leu Ala Val

Pro Thr Ser Lys Lys Lys Glu Thr

Glu Ser Ala Ile Tyr Ile Phe Ile

Ser Asp Thr Gly Arg Pro Phe Val

Glu Met Tyr Ser Glu Ile Pro Glu

Ile Ile His Met Thr Glu Gly Arg

Glu Leu Val Ile Pro Cys Arg Val

Thr Ser Pro Asn Ile Thr Val Thr

Leu Lys Lys Phe Pro Leu Asp Thr

Leu Ile Pro Asp Gly Lys Arg Ile

Ile Trp Asp Ser Arg Lys Gly Phe

Ile Ile Ser Asn Ala Thr Tyr Lys

Glu Ile Gly Leu Leu Thr Cys Glu

Ala Thr Val Asn Gly His Leu Tyr

Lys Thr Asn Tyr Leu Thr His Arg

Gln Thr Asn Thr Ile Ile Asp Val

Gln Ile Ser Thr Pro Arg Pro Val

Lys Leu Leu Arg Gly His Thr Leu

Val Leu Asn Cys Thr Ala Thr Thr

Pro Leu Asn Thr Arg Val Gln Met

Thr Trp Ser Tyr Pro Asp Glu Lys

Asn Lys Arg Ala Ser Val Arg Arg

Arg Ile Asp Gln Ser Asn Ser His

Ala Asn Ile Phe Tyr Ser Val Leu

Thr Ile Asp Lys Met Gln Asn Lys

Asp Lys Gly Leu Tyr Thr Cys Arg

Val Arg Ser Gly Pro Ser Phe Lys

Ser Val Asn Thr Ser Val His Ile

Tyr Asp Lys Ala Phe Ile Thr Val

Lys His Arg Lys Gln Gln Val Leu

Glu Thr Val Ala Gly Lys Arg Ser

Tyr Arg Leu Ser Met Lys Val Lys

Ala Phe Pro Ser Pro Glu Val Val

Trp Leu Lys Asp Gly Leu Pro Ala

Thr Glu Lys Ser Ala Arg Tyr Leu

Thr Arg Gly Tyr Ser Leu Ile Ile

Lys Asp Val Thr Glu Glu Asp Ala

Gly Asn Tyr Thr Ile Leu Leu Ser

Ile Lys Gln Ser Asn Val Phe Lys

Asn Leu Thr Ala Thr Leu Ile Val

Asn Val Lys Pro Gln Ile Tyr Glu

Lys Ala Val Ser Ser Phe Pro Asp

Pro Ala Leu Tyr Pro Leu Gly Ser

Arg Gln Ile Leu Thr Cys Thr Ala

Tyr Gly Ile Pro Gln Pro Thr Ile

Lys Trp Phe Trp His Pro Cys Asn

His Asn His Ser Glu Ala Arg Cys

Asp Phe Cys Ser Asn Asn Glu Glu

Ser Phe Ile Leu Asp Ala Asp Ser

Asn Met Gly Asn Arg Ile Glu Ser

Ile Thr Gln Arg Met Ala Ile Ile

Glu Gly Lys Asn Lys Met Ala Ser

Thr Leu Val Val Ala Asp Ser Arg

Ile Ser Gly Ile Tyr Ile Cys Ile

Ala Ser Asn Lys Val Gly Thr Val

Gly Arg Asn Ile Ser Phe Tyr Ile

Thr Asp Val Pro Asn Gly Phe His

Val Asn Leu Glu Lys Met Pro Thr

Glu Gly Glu Asp Leu Lys Leu Ser

Cys Thr Val Asn Lys Phe Leu Tyr

Arg Asp Val Thr Trp Ile Leu Leu

Arg Thr Val Asn Asn Arg Thr Met

His Tyr Ser Ile Ser Lys Gln Lys

Met Ala Ile Thr Lys Glu His Ser

Ile Thr Leu Asn Leu Thr Ile Met

Asn Val Ser Leu Gln Asp Ser Gly

Thr Tyr Ala Cys Arg Ala Arg Asn

Val Tyr Thr Gly Glu Glu Ile Leu

Gln Lys Lys Glu Ile Thr Ile Arg

Gly Glu His Cys Asn Lys Lys Ala

Val Phe Ser Arg Ile Ser Lys Phe

Lys Ser Thr Arg Asn Asp Cys Thr

Thr Gln Ser Asn Val Lys His.

4 . The soluble VEGF inhibitor of claim 2 corresponding to sVEGF-RI comprising the amino acid sequence:

Ser Lys Leu Lys Asp Pro Glu Leu

(SEQ. ID. NO.:12)

Ser Leu Lys Gly Thr Gln His Ile

Met Gln Ala Gly Gln Thr Leu His

Leu Gln Cys Arg Gly Glu Ala Ala

His Lys Trp Ser Leu Pro Glu Met

Val Ser Lys Glu Ser Glu Arg Leu

Ser Ile Thr Lys Ser Ala Cys Gly

Arg Asn Gly Lys Gln Phe Cys Ser

Thr Leu Thr Leu Asn Thr Ala Gln

Ala Asn His Thr Gly Phe Tyr Ser

Cys Lys Tyr Leu Ala Val Pro Thr

Ser Lys Lys Lys Glu Thr Glu Ser

Ala Ile Tyr Ile Phe Ile Ser Asp

Thr Gly Arg Pro Phe Val Glu Met

Tyr Ser Glu Ile Pro Glu Ile Ile

His Met Thr Glu Gly Arg Glu Leu

Val Ile Pro Cys Arg Val Thr Ser

Pro Asn Ile Thr Val Thr Leu Lys

Lys Phe Pro Leu Asp Thr Leu Ile

Pro Asp Gly Lys Arg Ile Ile Trp

Asp Ser Arg Lys Gly Phe Ile Ile

Ser Asn Ala Thr Tyr Lys Glu Ile

Gly Leu Leu Thr Cys Glu Ala Thr

Val Asn Gly His Leu Tyr Lys Thr

Asn Tyr Leu Thr His Arg Gln Thr

Asn Thr Ile Ile Asp Val Gln Ile

Ser Thr Pro Arg Pro Val Lys Leu

Leu Arg Gly His Thr Leu Val Leu

Asn Cys Thr Ala Thr Thr Pro Leu

Asn Thr Arg Val Gln Met Thr Trp

Ser Tyr Pro Asp Glu Lys Asn Lys

Arg Ala Ser Val Arg Arg Arg Ile

Asp Gln Ser Asn Ser His Ala Asn

Ile Phe Tyr Ser Val Leu Thr Ile

Asp Lys Met Gln Asn Lys Asp Lys

Gly Leu Tyr Thr Cys Arg Val Arg

Set Gly Pro Ser Phe Lys Ser Val

Asn Thr Set Val His Ile Tyr Asp

Lys Ala Phe Ile Thr Val Lys His

Arg Lys Gln Gln Val Leu Glu Thr

Val Ala Gly Lys Arg Ser Tyr Arg

Leu Ser Met Lys Val Lys Ala Phe

Pro Ser Pro Glu Val Val Trp Leu

Lys Asp Gly Leu Pro Ala Thr Glu

Lys Ser Ala Arg Tyr Leu Thr Arg

Gly Tyr Ser Leu Ile Ile Lys Asp

Val Thr Glu Glu Asp Ala Gly Asn

Tyr Thr Ile Leu Leu Set Ile Lys

Gln Ser Asn Val Phe Lys Asn Leu

Thr Ala Thr Leu Ile Val Asn Val

Lys Pro Gln Ile Tyr Glu Lys Ala

Val Ser Ser Phe Pro Asp Pro Ala

Leu Tyr Pro Leu Gly Ser Atg Gln

Ile Leu Thr Cys Thr Ala Tyr Gly

Ile Pro Gln Pro Thr Ile Lys Trp

Phe Trp His Pro Cys Asn His Asn

His Ser Glu Ala Arg Cys Asp Phe

Cys Ser Asn Asn Glu Glu Ser Phe

Ile Leu Asp Ala Asp Ser Asn Met

Gly Asn Arg Ile Glu Ser Ile Thr

Gln Atg Met Ala Ile Ile Glu Gly

Lys Asn Lys Met Ala Ser Thr Leu

Val Val Ala Asp Ser Arg Ile Ser

Gly Ile Tyr Ile Cys Ile Ala Ser

Asn Lys Val Gly Thr Val Gly Arg

Asn Ile Ser Phe Tyr Ile Thr Asp

Val Pro Asn Gly Phe His Val Asn

Leu Glu Lys Met Pro Thr Glu Gly

Glu Asp Leu Lys Leu Ser Cys Thr

Val Asn Lys Phe Leu Tyr Arg Asp

Val Thr Trp Ile Leu Leu Arg Thr

Val Asn Asn Arg Thr Met His Tyr

Ser Ile Ser Lys Gln Lys Met Ala

Ile Thr Lys Glu His Set Ile Thr

Leu Asn Leu Thr Ile Met Asn Val

Ser Leu Gln Asp Ser Gly Thr Tyr

Ala Cys Arg Ala Arg Asn Val Tyr

Thr Gly Glu Glu Ile Leu Gln Lys

Lys Glu Ile Thr Ile Arg Gly Glu

His Cys Asn Lys Lys Ala Val Phe

Ser Arg Ile Set Lys Phe Lys Set

Thr Arg Asn Asp Cys Thr Thr Gln

Set Asn Val Lys His.

5 . The soluble VEGF inhibitor of claim 2 corresponding to sVEGF-RII comprising the amino acid sequence:

MQSKVLLAVALWLCVETRAASVGLPSVSLDLP

(SEQ. ID. NO.:13)

RLSIQKDILTIKANTTLQITCRGQRDLDWLWP

NNQSGSEQRVEVTECSDGLFCKTLTIPKVIGN

DTGAYKCFYRETDLASVIYVYVQDYRSPFIAS

VSDQHGVVYITENKNKTVVIPCLGSISNLNVS

LCARYPEKRFVPDGNRISWDSKKGFTIPSYMI

SYAGMVFCEAKINDESYQSIMYIVVVVGYRIY

DVVLSPSHGIELSVGEKLVLNCTARTELNVGI

DFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKF

LSTLTIDGVTRSDQGLYTCAASSGLMTKKNST

FVRVHEKPFVAFGSGMESLVEATVGERVRIPA

KYLGYPPPEIKWYKNGIPLESNHTIKAGHVLT

IMEVSERDTGNYTVILTNPISKEKQSHVVSLV

VYVPPQIGEKSLISPVDSYQYGTTQTLTCTVY

AIPPPHHIHWYWQLEEECANEPSQAVSVTNPY

PCEEWRSVEDFQGGNKIAVNKNQFALIEGKNK

TVSTLVIQAANVSALYKCEAVNKVGRGERVIS

FHVTRGPEITLQPDMQPTEQESVSLWCTADRS

TFENLTWYKLGPQPLPIHVGELPTPVCKNLDT

LWKLNATMFSNSTNDILIMELKNASLQDQGDY

VCLAQDRKTKKRHCVVRQLTVLER.

6 . The soluble VEGF inhibitor of claim 2 corresponding to sVEGF-RTMI comprising the amino acid sequence:

MVSYWDTGVLLCALLSCLLLTGSSSGSKLKDP

(SEQ. ID. NO.:14)

ELSLKGTQHIMQAGQTLHLQCRGEAAHKWSLP

EMVSKESERLSITKSACGRNGKQFCSTLTLNT

AQANHTGFYSCKYLAVPTSKKKETESAIYIFI

SDTGRPFVEMYSEIPEIIHMTEGRELVIPCRV

TSPNITVTLKKFPLDTLIPDGKRIIWDSRKGF

IISNATYKEIGLLTCEATVNGHLYKTNYLTHR

QTNTIIDVQISTPRPVKLLRGHTLVLNCTATT

PLNTRVQMTWSYPDEKNKRASVRRRIDQSNSH

ANIFYSVLTIDKMQNKDKGLYTCRVRSGPSFK

SVNTSVHIYDKAFITVKHRKQQVLETVAGKRS

YRLSMKVKAFPSPEVVWLKDGLPATEKSARYL

TRGYSLIIKDVTEEDAGNYTILLSIKQSNVFK

NLTATLIVNVKPQIYEKAVSSFPDPALYPLGS

RQILTCTAYGIPQPTIKWFWHPCNHNHSEARC

DFCSNNEESFILDADSNMGNRIESITQRMAII

EGKNKMASTLVVADSRISGIYICIASNKVGTV

GRNISFYITDVPNGFHVNLEKMPTEGEDLKLS

CTVNKFLYRDVTWILLRTVNNRTMHYSISKQK

MAITKEHSITLNLTIMNVSLQDSGTYACRARN

VYTGEEILQKKEITIRDQEAPYLLRNLSDHTV

AISSSTTLDCHANGVPEPQITWFKNNHKIQQE

PGIILGPGSSTLFIERVTEEDEGVYHCKATNQ

KGSVESSAYLTVQGTSDKSNLELITLTCTCVA

ATLFWLLLTLLI.

7 . The soluble VEGF inhibitor of claim 2 corresponding to sVEGF-RTMII comprising the amino acid sequence:

MQSKVLLAVALWLCVETRAASVGLPSVSLDLP

(SEQ. ID. NO.:15)

RLSIQKDILTIKANTTLQITCRGQRDLDWLWP

NNQSGSEQRVEVTECSDGLFCKTLTIPKVIGN

DTGAYKCFYRETDLASVIYVYVQDYRSPFIAS

VSDQHGVVYITENKNKTVVIPCLGSISNLNVS

LCARYPEKRFVPDGNRISWDSKKGFTIPSYMI

SYAGMVFCEAKINDESYQSIMYIVVVVGYRIY

DVVLSPSHGIELSVGEKLVLNCTARTELNVGI

DFNWEYPSSKHQHKKLVNRDLKTQSGSEMKKF

LSTLTIDGVTRSDQGLYTCAASSGLMTKKNST

FVRVHEKPFVAFGSGMESLVEATVGERVRIPA

KYLGYPPPEIKWYKNGIPLESNHTIKAGHVLT

IMEVSERDTGNYTVILTNPISKEKQSHVVSLV

VYVPPQIGEKSLISPVDSYQYGTTQTLTCTVY

AIPPPHHIHWYWQLEEECANEPSQAVSVTNPY

PCEEWRSVEDFQGGNKIAVNKNQFALIEGKNK

TVSTLVIQAANVSALYKCEAVNKVGRGERVIS

FHVTRGPEITLQPDMQPTEQESVSLWCTADRS

TFENLTWYKLGPQPLPIHVGELPTPVCKNLDT

LWKLNATMFSNSTNDILIMELKNASLQDQGDY

VCLAQDRKTKKRHCVVRQLTVLERVAPTITGN

LENQTTSIGESIEVSCTASGNPPPQIMWFKDN

ETLVEDSGIVLKDGNRNLTIRRVRKEDEGLYC

QACSVLGCAKVEAFFIIEGAQEKTNLEIIILV

GTTVIAMFFWLLLVIILGTV.

8 . An expression vector comprising a promoter, and a DNA sequence encoding a soluble VEGF inhibitor for expression in recombinant host cells wherein the soluble VEGF inhibitor is selected from the group consisting of sVEGF-RI, sVEGF-RII, sVEGF-RTMI and sVEGF-RTMII.

9 . The expression vector of claim 8 wherein the DNA encoding the sVEGF-RI comprises the nucleotide sequence:

GCGGACACTCCTCTCGGCTCCTCCCCGGCAGCGG

(SEQ. ID. NO.:5)

CGGCGGCTCGGAGCGGGCTCCGGGGCTCGGGTGC

AGCGGCCAGCGGGCCTGGCGGCGAGGATTACCCG

GGGAAGTGGTTGTCTCCTGGCTGGAGCCGCGAGA

CGGGCGCTCAGGGCGCGGGGCCGGCGGCGGCGAA

CGAGAGGACGGACTCTGGCGGCCGGGTCGTTGGC

CGGGGGAGCGCGGGCACCGGGCGAGCAGGCCGCG

TCGCGCTCACC ATG GTC AGC TAC TGG

GAC ACC GGG GTC CTG CTG TGC GCG

CTG CTC AGC TGT CTG CTT CTC ACA

GGA TCT AGT TCA GGT TCA AAA TTA

AAA GAT CCT GAA CTG AGT TTA AAA

GGC ACC CAG CAC ATC ATG CAA GCA

GGC CAG ACA CTG CAT CTC CAA TGC

AGG GGG GAA GCA GCC CAT AAA TGG

TCT TTG CCT GAA ATG GTG AGT AAG

GAA AGC GAA AGG CTG AGC ATA ACT

AAA TCT GCC TGT GGA AGA AAT GGC

AAA CAA TTC TGC AGT ACT TTA ACC

TTG AAC ACA GCT CAA GCA AAC CAC

ACT GGC TTC TAC AGC TGC AAA TAT

CTA GCT GTA CCT ACT TCA AAG AAG

AAG GAA ACA GAA TCT GCA ATC TAT

ATA TTT ATT AGT GAT ACA GGT AGA

CCT TTC GTA GAG ATG TAC AGT GAA

ATC CCC GAA ATT ATA CAC ATG ACT

GAA GGA AGG GAG CTC GTC ATT CCC

TGC CGG GTT ACG TCA CCT AAC ATC

ACT GTT ACT TTA AAA AAG TTT CCA

CTT GAC ACT TTG ATC CCT GAT GGA

AAA CGC ATA ATC TGG GAC AGT AGA

AAG GGC TTC ATC ATA TCA AAT GCA

ACG TAC AAA GAA ATA GGG CTT CTG

ACC TGT GAA GCA ACA GTC AAT GGG

CAT TTG TAT AAG ACA AAC TAT CTC

ACA CAT CGA CAA ACC AAT ACA ATC

ATA GAT GTC CAA ATA AGC ACA CCA

CGC CCA GTC AAA TTA CTT AGA GGC

CAT ACT CTT GTC CTC AAT TGT ACT

GCT ACC ACT CCC TTG AAC ACG AGA

GTT CAA ATG ACC TGG AGT TAC CCT

GAT GAA AAA AAT AAG AGA GCT TCC

GTA AGG CGA CGA ATT GAC CAA AGC

AAT TCC CAT GCC AAC ATA TTC TAC

AGT GTT CTT ACT ATT GAC AAA ATG

CAG AAC AAA GAC AAA GGA CTT TAT

ACT TGT CGT GTA AGG AGT GGA CCA

TCA TTC AAA TCT GTT AAC ACC TCA

GTG CAT ATA TAT GAT AAA GCA TTC

ATC ACT GTG AAA CAT CGA AAA CAG

CAG GTG CTT GAA ACC GTA GCT GGC

AAG CGG TCT TAC CGG CTC TCT ATG

AAA GTG AAG GCA TTT CCC TCG CCG

GAA GTT GTA TGG TTA AAA GAT GGG

TTA CCT GCG ACT GAG AAA TCT GCT

CGC TAT TTG ACT CGT GGC TAC TCG

TTA ATT ATC AAG GAC GTA ACT GAA

GAG GAT GCA GGG AAT TAT ACA ATC

TTG CTG AGC ATA AAA CAG TCA AAT

GTG TTT AAA AAC CTC ACT GCC ACT

CTA ATT GTC AAT GTG AAA CCC CAG

ATT TAC GAA AAG GCC GTG TCA TCG

TTT CCA GAC CCG GCT CTC TAC CCA

CTG GGC AGC AGA CAA ATC CTG ACT

TGT ACC GCA TAT GGT ATC CCT CAA

CCT ACA ATC AAG TGG TTC TGG CAC

CCC TGT AAC CAT AAT CAT TCC GAA

GCA AGG TGT GAC TTT TGT TCC AAT

AAT GAA GAG TCC TTT ATC CTG GAT

GCT GAC AGC AAC ATG GGA AAC AGA

ATT GAG AGC ATC ACT CAG CGC ATG

GCA ATA ATA GAA GGA AAG AAT AAG

ATG GCT AGC ACC TTG GTT GTG GCT

GAC TCT AGA ATT TCT GGA ATC TAC

ATT TGC ATA GCT TCC AAT AAA GTT

GGG ACT GTG GGA AGA AAC ATA AGC

TTT TAT ATC ACA GAT GTG CCA AAT

GGG TTT CAT GTT AAC TTG GAA AAA

ATG CCG ACG GAA GGA GAG GAC CTG

AAA CTG TCT TGC ACA GTT AAC AAG

TTC TTA TAC AGA GAC GTT ACT TGG

ATT TTA CTG CGG ACA GTT AAT AAC

AGA ACA ATG CAC TAC AGT ATT AGC

AAG CAA AAA ATG GCC ATC ACT AAG

GAG CAC TCC ATC ACT CTT AAT CTT

ACC ATC ATG AAT GTT TCC CTG CAA

GAT TCA GGC ACC TAT GCC TGC AGA

GCC AGG AAT GTA TAC ACA GGG GAA

GAA ATC CTC CAG AAG AAA GAA ATT

ACA ATC AGA GGT GAG CAC TGC AAC

AAA AAG GCT GTT TTC TCT CGG ATC

TCC AAA TTT AAA AGC ACA AGG AAT

GAT TGT ACC ACA CAA AGT AAT GTA

AAA CAT TAA AGGACTCATTAAAAAGTAACAG

TTGTCTCATATCATCTTGATTTATTGTCACTGTT

GCTAACTTTCAGGCTCGGAGGAGATGCTCCTCCC

AAAATGAGTTCGGAGATGATAGCAGTAATAATGA

GACCCCCGGGCTCCAGCTCTGGGCCCCCCATTCA

GGCCGAGGGGGCTGCTCCGGGGGGCCGACTTGGT

GCACGTTTGGATTTGGAGGATCCCTGCACTGCCT

TCTCTGTGTTTGTTGCTCTTGCTGTTTTCTCCTG

CCTGATAAACAACAACTTGGGATGATCCTTTCCA

TTTTGATGCCAACCTCTTTTTATTTTTAAGCGGC

GCCCTATAGT.

10 . The expression vector of claim 8 wherein the DNA encoding the sVEGF-RII comprises the nucleotide sequence:

GGTGTGGTCGCTGCGTTTCCTCTGCCTGCGCC

(SEQ. ID. NO.:16)

GGGCATCACTTGCGCGCCGCAGAAAGTCCGTC

TGGCAGCCTGGATATCCTCTCCTACCGGCACC

CGCAGACGCCCCTGCAGCCGCGGTCGGCGCCC

GGGCTCCCTAGCCCTGTGCGCTCAACTGTCCT

GCGCTGCGGGGTGCCGCGAGTTCCACCTCCGC

GCCTCCTTCTCTAGACAGGCGCTGGGAGAAAG

AACCGGCTCCCGAGTTCCGGCATTTCGCCCGG

CTCGAGGTGCAGGATGCAGAGCAAGGTGCTGC

TGGCCGTCGCCCTGTGGCTCTGCGTGGAGACC

CGGGCCGCCTCTGTGGGTTTGCCTAGTGTTTC

TCTTGATCTGCCCAGGCTCAGCATACAAAAAG

ACATACTTACAATTAAGGCTAATACAACTCTT

CAAATTACTTGCAGGGGACAGAGGGACTTGGA

CTGGCTTTGGCCCAATAATCAGAGTGGCAGTG

AGCAAAGGGTGGAGGTGACTGAGTGCAGCGAT

GGCCTCTTCTGTAAGACACTCACAATTCCAAA

AGTGATCGGAAATGACACTGGAGCCTACAAGT

GCTTCTACCGGGAAACTGACTTGGCCTCGGTC

ATTTATGTCTATGTTCAAGATTACAGATCTCC

ATTTATTGCTTCTGTTAGTGACCAACATGGAG

TCGTGTACATTACTGAGAACAAAAACAAAACT

GTGGTGATTCCATGTCTCGGGTCCATTTCAAA

TCTCAACGTGTCACTTTGTGCAAGATACCCAG

AAAAGAGATTTGTTCCTGATGGTAACAGAATT

TCCTGGGACAGCAAGAAGGGCTTTACTATTCC

CAGCTACATGATCAGCTATGCTGGCATGGTCT

TCTGTGAAGCAAAAATTAATGATGAAAGTTAC

CAGTCTATTATGTACATAGTTGTCGTTGTAGG

GTATAGGATTTATGATGTGGTTCTGAGTCCGT

CTCATGGAATTGAACTATCTGTTGGAGAAAAG

CTTGTCTTAAATTGTACAGCAAGAACTGAACT

AAATGTGGGGATTGACTTCAACTGGGAATACC

CTTCTTCGAAGCATCAGCATAAGAAACTTGTA

AACCGAGACCTAAAAACCCAGTCTGGGAGTGA

GATGAAGAAATTTTTGAGCACCTTAACTATAG

ATGGTGTAACCCGGAGTGACCAAGGATTGTAC

ACCTGTGCAGCATCCAGTGGGCTGATGACCAA

GAAGAACAGCACATTTGTCAGGGTCCATGAAA

AACCTTTGTTGCTTTTGGAAGTGGCATGGAAT

CTCTGGTGGAAGCCACGGTGGGGGAGCGTGTC

AGAATCCCTGCGAAGTACCTTGGTTACCCACC

CCCAGAAATAAAATGGTATAAAAATGGAATAC

CCCTTGAGTCCAATCACACAATTAAAGCGGGG

CATGTACTGACGATTATGGAAGTGAGTGAAAG

AGACACAGGAAATTACACTGTCATCCTTACCA

ATCCCATTTCAAAGGAGAAGCAGAGCCATGTG

GTCTCTCTGGTTGTGTATGTCCCACCCCAGAT

TGGTGAGAAATCTCTAATCTCTCCTGTGGATT

CCTACCAGTACGGCACCACTCAAACGCTGACA

TGTACGGTCTATGCCATTCCTCCCCCGCATCA

CATCCACTGGTATTGGCAGTTGGAGGAAGAGT

GCGCCAACGAGCCCAGCCAAGCTGTCTCAGTG

ACAAACCCATACCCTTGTGAAGAATGGAGAAG

TGTGGAGGACTTCCAGGGAGGAAATAAAATTG

CCGTTAATAAAAATCAATTTGCTCTAATTGAA

GGAAAAAACAAAACTGTAAGTACCCTTGTTAT

CCAAGCGGCAAATGTGTCAGCTTTGTACAAAT

GTGAAGCGGTCAACAAAGTCGGGAGAGGAGAG

AGGGTGATCTCCTTCCACGTGACCAGGGGTCC

TGAAATTACTTTGCAACCTGACATGCAGCCCA

CTGAGCAGGAGAGCGTGTCTTTGTGGTGCACT

GCAGACAGATCTACGTTTGAGAACCTCACATG

GTACAAGCTTGGCCCACAGCCTCTGCCAATCC

ATGTGGGAGAGTTGCCCACACCTGTTTGCAAG

AACTTGGATACTCTTTGGAAATTGAATGCCAC

CATGTTCTCTAATAGCACAAATGACATTTTGA

TCATGGAGCTTAAGAATGCATCCTTGCAGGAC

CAAGGAGACTATGTCTGCCTTGCTCAAGACAG

GAAGACCAAGAAAAGACATTGCGTGGTCAGGC

AGCTCACAGTCCTAGAGCGTTAA.

11 . The expression vector of claim 8 wherein the DNA encoding the sVEGF-RTMI comprises the nucleotide sequence:

GCGCTCACCATGGTCAGCTACTGGGACACCGG

(SEQ. ID. NO.:17)

GGTCCTGCTGTGCGCGCTGCTCAGCTGTCTGC

TTCTCACAGGATCTAGTTCAGGTTCAAAATTA

AAAGATCCTGAACTGAGTTTAAAAGGCACCCA

GCACATCATGCAAGCAGGCCAGACACTGCATC

TCCAATGCAGGGGGGAAGCAGCCCATAAATGG

TCTTTGCCTGAAATGGTGAGTAAGGAAAGCGA

AAGGCTGAGCATAACTAAATCTGCCTGTGGAA

GAAATGGCAAACAATTCTGCAGTACTTTAACC

TTGAACACAGCTCAAGCAAACCACACTGGCTT

CTACAGCTGCAAATATCTAGCTGTACCTACTT

CAAAGAAGAAGGAAACAGAATCTGCAATCTAT

ATATTTATTAGTGATACAGGTAGACCTTTCGT

AGAGATGTACAGTGAAATCCCCGAAATTATAC

ACATGACTGAAGGAAGGGAGCTCGTCATTCCC

TGCCGGGTTACGTCACCTAACATCACTGTTAC

TTTAAAAAAGTTTCCACTTGACACTTTGATCC

CTGATGGAAAACGCATAATCTGGGACAGTAGA

AAGGGCTTCATCATATCAAATGCAACGTACAA

AGAAATAGGGCTTCTGACCTGTGAAGCAACAG

TCAATGGGCATTTGTATAAGACAAACTATCTC

ACACATCGACAAACCAATACAATCATAGATGT

CCAAATAAGCACACCACGCCCAGTCAAATTAC

TTAGAGGCCATACTCTTGTCCTCAATTGTACT

GCTACCACTCCCTTGAACACGAGAGTTCAAAT

GACCTGGAGTTACCCTGATGAAAAAAATAAGA

GAGCTTCCGTAAGGCGACGAATTGACCAAAGC

AATTCCCATGCCAACATATTCTACAGTGTTCT

TACTATTGACAAAATGCAGAACAAAGACAAAG

GACTTTATACTTGTCGTGTAAGGAGTGGACCA

TCATTCAAATCTGTTAACACCTCAGTGCATAT

ATATGATAAAGCATTCATCACTGTGAAACATC

GAAAACAGCAGGTGCTTGAAACCGTAGCTGGC

AAGCGGTCTTACCGGCTCTCTATGAAAGTGAA

GGCATTTCCCTCGCCGGAAGTTGTATGGTTAA

AAGATGGGTTACCTGCGACTGAGAAATCTGCT

CGCTATTTGACTCGTGGCTACTCGTTAATTAT

CAAGGACGTAACTGAAGAGGATGCAGGGAATT

ATACAATCTTGCTGAGCATAAAACAGTCAAAT

GTGTTTAAAAACCTCACTGCCACTCTAATTGT

CAATGTGAAACCCCAGATTTACGAAAAGGCCG

TGTCATCGTTTCCAGACCCGGCTCTCTACCCA

CTGGGCAGCAGACAAATCCTGACTTGTACCGC

ATATGGTATCCCTCAACCTACAATCAAGTGGT

TCTGGCACCCCTGTAACCATAATCATTCCGAA

GCAAGGTGTGACTTTTGTTCCAATAATGAAGA

GTCCTTTATCCTGGATGCTGACAGCAACATGG

GAAACAGAATTGAGAGCATCACTCAGCGCATG

GCAATAATAGAAGGAAAGAATAAGATGGCTAG

CACCTTGGTTGTGGCTGACTCTAGAATTTCTG

GAATCTACATTTGCATAGCTTCCAATAAAGTT

GGGACTGTGGGAAGAAACATAAGCTTTTATAT

CACAGATGTGCCAAATGGGTTTCATGTTAACT

TGGAAAAAATGCCGACGGAAGGAGAGGACCTG

AAACTGTCTTGCACAGTTAACAAGTTCTTATA

CAGAGACGTTACTTGGATTTTACTGCGGACAG

TTAATAACAGAACAATGCACTACAGTATTAGC

AAGCAAAAAATGGCCATCACTAAGGAGCACTC

CATCACTCTTAATCTTACCATCATGAATGTTT

CCCTGCAAGATTCAGGCACCTATGCCTGCAGA

GCCAGGAATGTATACACAGGGGAAGAAATCCT

CCAGAAGAAAGAAATTACAATCAGAGATCAGG

AAGCACCATACCTCCTGCGAAACCTCAGTGAT

CACACAGTGGCCATCAGCAGTTCCACCACTTT

AGACTGTCATGCTAATGGTGTCCCCGAGCCTC

AGATCACTTGGTTTAAAAACAACCACAAAATA

CAACAAGAGCCTGGAATTATTTTAGGACCAGG

AAGCAGCACGCTGTTTATTGAAAGAGTCACAG

AAGAGGATGAAGGTGTCTATCACTGCAAAGCC

ACCAACCAGAAGGGCTCTGTGGAAAGTTCAGC

ATACCTCACTGTTCAAGGAACCTCGGACAAGT

CTAATCTGGAGCTGATCACTCTAACATGCACC

TGTGTGGCTGCGACTCTCTTCTGGCTCCTATT

AACCCTCCTTATCTAA.

12 . The expression vector of claim 8 wherein the DNA encoding the sVEGF-RTMII comprises the nucleotide sequence:

(SEQ. ID. NO.: 18)

CTCGAGGTGCAGGATGCAGAGCAAGGTGCTGCTGGCCGTCGCCCTGTGGC

TCTGCGTGGAGACCCGGGCCGCCTCTGTGGGTTTGCCTAGTGTTTCTCTT

GATCTGCCCAGGCTCAGCATACAAAAAGACATACTTACAATTAAGGCTAA

TACAACTCTTCAAATTACTTGCAGGGGACAGAGGGACTTGGACTGGCTTT

GGCCCAATAATCAGAGTGGCAGTGAGCAAAGGGTGGAGGTGACTGAGTGC

AGCGATGGCCTCTTCTGTAAGACACTCACAATTCCAAAAGTGATCGGAAA

TGACACTGGAGCCTACAAGTGCTTCTACCGGGAAACTGACTTGGCCTCGG

TCATTTATGTCTATGTTCAAGATTACAGATCTCCATTTATTGCTTCTGTT

AGTGACCAACATGGAGTCGTGTACATTACTGAGAACAAAAACAAAACTGT

GGTGATTCCATGTCTCGGGTCCATTTCAAATCTCAACGTGTCACTTTGTG

CAAGATACCCAGAAAAGAGATTTGTTCCTGATGGTAACAGAATTTCCTGG

GACAGCAAGAAGGGCTTTACTATTCCCAGCTACATGATCAGCTATGCTGG

CATGGTCTTCTGTGAAGCAAAAATTAATGATGAAAGTTACCAGTCTATTA

TGTACATAGTTGTCGTTGTAGGGTATAGGATTTATGATGTGGTTCTGAGT

CCGTCTCATGGAATTGAACTATCTGTTGGAGAAAAGCTTGTCTTAAATTG

TACAGCAAGAACTGAACTAAATGTGGGGATTGACTTCAACTGGGAATACC

CTTCTTCGAAGCATCAGCATAAGAAACTTGTAAACCGAGACCTAAAAACC

CAGTCTGGGAGTGAGATGAAGAAATTTTTGAGCACCTTAACTATAGATGG

TGTAACCCGGAGTGACCAAGGATTGTACACCTGTGCAGCATCCAGTGGGC

TGATGACCAAGAAGAACAGCACATTTGTCAGGGTCCCATGAAAAACCTTT

GTTGCTTTTGGAAGTGGCATGGAATCTCTGGTGGAAGCCACGGTGGGGGA

GCGTGTCAGAATCCCTGCGAAGTACCTTGGTTACCCACCCCCAGAAATAA

AATGGTATAAAAATGGAATACCCCTTGAGTCCAATCACACAATTAAAGCG

GGGCATGTACTGACGAATATGGAAGTGAGTGAAAGAGACACAGGAAATTA

CACTGTCATCCTTACCAATCCCATTTCAAAGGAGAAGCAGAGCCATGTGG

TCTCTCTGGTTGTGTATGTCCCACCCCAGATTGGTGAGAAATCTCTAATC

TCTCCTGTGGATTCCTACCAGTACGGCACCACTCAAACGCTGACATGTAC

GGTCTATGCCATTCCTCCCCCGCATCACATCCACTGGTATTGGCAGTTGG

AGGAAGAGTGCGCCAACGAGCCCAGCCAAGCTGTCTCAGTGACAAACCCA

TACCCTTGTGAAGAATGGAGAAGTGTGGAGGACTTCCAGGGAGGAAATAA

AATTGCCGTTAATAAAAATCAATTTGCTCTAATTGAAGGAAAAAACAAAA

CTGTAAGTACCCTTGTTATCCAAGCGGCAAATGTGTCAGCTTTGTACAAA

TGTGAAGCGGTCAACAAAGTCGGGAGAGGAGAGAGGGTCTGACATGCAGC

CCACTGAGCAGGAGAGCGTGTCTTTGTGGTGCACTGCAGACAGATCTACG

TTTGAGAACCTCACATGGTACAAGCTTGGCCCACAGCCTCTGCCAATCCA

TGTGGGAGAGTTGCCCACACCTGTTTGCAAGAACTTGGATACTCTTTGGA

AATTGAATGCCACCATGTTCTCTAATAGCACAAATGACATTTTGATCATG

GAGCTTAAGAATGCATCCTTGCAGGACCAAGGAGACTATGTCTGCCTTGC

TCAAGACAGGAAGACCAAGAAAAGACATTGCGTGGTCAGGCAGCTCACAG

TCCTAGAGCGTGTGGCACCCACGATCACAGGAAACCTGGAGAATCAGACG

ACAAGTATTGGGGAAAGCATCGAAGTCTCATGCACGGCATCTGGGAATCC

CCCTCCACAGATCATGTGGTTTAAAGATAATGAGACCCTTGTAGAAGACT

CAGGCATTGTATTGAAGGATGGGAACCGGAACCTCACTATCCGCAGAGTG

AGGAAGGAGGACGAAGGCCTCTACACCTGCCAGGCATGCAGTGTTCTTGG

CTGTGCAAAAGTGGAGGCATTTTTCATAATAGAAGGTGCCCAGGAAAAGA

CGAACTTGGAAATCATTATTCTAGTAGGCACGACGGTGATTGCCATGTTC

TTCTGGCTACTTCTTGTCATCATCCTAGGGACCGTTTAA.

13 . A recombinant host cell containing the expression vector of claim 8 .

14 . A method for inhibiting VEGF receptor function comprising the administration of the VEGF inhibitor of claim 1 in an amount sufficient to inhibit VEGF receptor function.

15 . The method of claim 14 wherein the VEGF inhibitor is selected from the group consisting of sVEGF-RI, sVEGF-RII, sVEGF-RTMI, and sVEGF-RTMII.

16 . A pharmaceutical composition comprising the inhibitor of claim 1 and a pharmaceutically acceptable carrier.

17 . The pharmaceutical composition of claim 16 wherein the inhibitor is selected from the group consisting of sVEGF-RI, sVEGF-RII, sVEGF-RTMI, and sVEGF-RTMII.

18 . A method for inhibiting angiogenesis comprising the administration of the VEGF inhibitor of claim 1 in an amount sufficient to inhibit angiogensis.