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Description
【特許請求の範囲】
【請求項１】 被検体における脈管形成障害治療の有効性を評価する方法において、
ａ）試験細胞集団においてＰＡ：１−２７からなる群から選択された１又は複数の核酸配列の発現を検出し、
ｂ）試験細胞集団における核酸配列の発現を、脈管形成段階が知られた細胞を少なくとも１つ含む参照細胞集団における核酸配列の発現と比較し、
ｃ）存在する場合には、試験細胞集団及び参照細胞集団における、ＰＡ：１−２７配列の発現レベルにおける差異を同定し、それにより被検体の脈管形成障害治療の有効性を評価することを含む方法。
【請求項２】 被検体における脈管形成障害を診断する又は脈管形成障害に対する感受性を決定する方法において、
ａ）試験細胞集団においてＰＡ：１−２７からなる群から選択された１又は複数の核酸配列の発現を検出し、
ｂ）試験細胞集団における核酸配列の発現を、脈管形成段階が知られた細胞を少なくとも１つ含む参照細胞集団における核酸配列の発現と比較し、
ｃ）存在する場合には、試験細胞集団及び参照細胞集団における、ＰＡ：１−２７配列の発現レベルにおける差異を同定し、それにより被検体の脈管形成障害を診断する又は脈管形成障害に対する感受性を決定することを含む方法。
【請求項３】 被検体における脈管形成障害治療のための試験治療薬を同定する方法において、
ａ）ＰＡ：１−２７からなる群の一又は複数の核酸配列を発現することができる試験細胞集団を試験治療薬と接触させ；
ｂ）試験治療薬と接触させた前記試験細胞集団における１又は複数の核酸配列の発現を検出し；
ｃ）試験細胞集団における核酸配列の発現を、脈管形成段階が知られた細胞を少なくとも１つ含む参照細胞集団における核酸配列の発現と比較し；そして、
ｄ）存在する場合には、試験治療薬と接触させた試験細胞集団及び参照細胞集団における、ＰＡ：１−２７配列の発現レベルにおける差異を同定し、それにより被検体の脈管形成障害治療のための試験治療薬を同定することを含む方法。
【請求項４】 試験治療薬が既知の抗-脈管形成障害薬である請求項３に記載の方法。
【請求項５】 試験治療薬が天然ＰＡポリペプチドのアゴニストである請求項３に記載の方法。
【請求項６】 試験治療薬が天然ＰＡポリペプチドのアンタゴニストである請求項３に記載の方法。
【請求項７】 アゴニストが抗-ＰＡ抗体である請求項５に記載の方法。
【請求項８】 アンタゴニストが抗-ＰＡ抗体である請求項６に記載の方法。
【請求項９】 試験治療薬が未知の抗-脈管形成障害薬である請求項３に記載の方法。
【請求項１０】 脈管形成障害が、脈管腫瘍、増殖性硝子体網膜症、慢性関節リウマチ、クローン病、アテローム性硬化症、卵巣過刺激、乾癬、新血管形成を伴う子宮内膜症、バルーン血管形成術に続く再狭窄、瘢痕組織の過形成、末梢脈管障害、高血圧、炎症性脈管炎、レイノルズ病及びレイノルズ現象、動脈瘤、動脈性再狭窄、血栓性静脈炎、リンパ管炎、リンパ浮腫、創傷治癒及び組織再生、虚血性再灌流障害、アンギナ、心筋梗塞、慢性心臓異常、鬱血性心不全等の心不全、加齢黄斑変性、及び骨粗鬆症からなる群から選択される請求項１ないし９の何れか一に記載の方法。
【請求項１１】 前記脈管形成障害が、乳癌、腎臓細胞上皮癌、扁平上皮癌、大腸上皮癌及び前立腺上皮癌からなる群から選択される癌である請求項１ないし９の何れか一に記載の方法。
【請求項１２】 試験細胞集団における核酸配列の発現が、参照細胞集団に比較して増加する請求項１ないし３の何れか一に記載の方法。
【請求項１３】 試験細胞集団における核酸配列の発現が、参照細胞集団に比較して減少する請求項１ないし３の何れか一に記載の方法。
【請求項１４】 試験細胞集団がインビトロで供給される請求項１ないし５の何れか一に記載の方法。
【請求項１５】 試験細胞集団が、哺乳動物被検体からエキソビボで供給される請求項１ないし５の何れか一に記載の方法。
【請求項１６】 被検体が哺乳動物である請求項１ないし１５の何れか一に記載の方法。
【請求項１７】 被検体がヒトである請求項１６に記載の方法。
【請求項１８】 脈管形成障害に罹患した又は発症する危険のある患者の脈管形成障害の治療のための医薬であって、ＰＡ：１−２７からなる群から選択される１又は複数の核酸配列の発現又は活性を変調させる薬剤を含有してなる医薬。
【請求項１９】 前記薬剤が、ＰＡ：５、１４及び１５からなる群から選択される１又は複数の核酸配列の発現又は活性を減少させる請求項１８に記載の医薬。
【請求項２０】 前記薬剤が、ＰＡ：１−４、６−１３及び１６−２６からなる群から選択される１又は複数の核酸配列の発現又は活性を増加させる請求項１８に記載の医薬。
【請求項２１】 薬剤が、ＰＡ核酸配列によりコードされるポリペプチドに対する抗体、アンチセンス核酸分子、ペプチド、ＰＡ ポリペプチドアゴニスト、ＰＡポリペプチドアンタゴニスト、ペプチド類似物、小分子、又は他の薬物である請求項１８に記載の医薬。
【請求項２２】 脈管形成障害が、心肥大、外傷、加齢黄斑変性、及び癌からなる群から選択される請求項１８に記載の医薬。
【請求項２３】 ＰＡ：１−２７からなる群から選択される２又はそれ以上の核酸配列を検出するための１又は複数の試薬を含んでなるキット。
【請求項２４】 プローブ核酸のアレーであって、前記プローブ核酸がＰＡ：１−２７からなる群から選択される２又はそれ以上の核酸配列を検出するアレー。
【請求項２５】 被検体における脈管形成障害を治療するために使用される単離されたポリペプチドであって、
ａ）ＰＡ：１−２７のアミノ酸配列を含むポリペプチド；
ｂ）ＰＡ：１−２７のアミノ酸配列を含むポリペプチドの断片であって、ＰＡ：１−２７の少なくとも６の連続するアミノ酸を含む断片；
ｃ）ＰＡ：１−２７のアミノ酸配列を含むポリペプチドの誘導体；
ｄ）ＰＡ：１−２７のアミノ酸配列を含むポリペプチドの類似物；及び
ｅ）ＰＡ：１−２７のアミノ酸配列を含むポリペプチドの相同体
からなる群から選択されるポリペプチドと少なくとも８０％同一のポリペプチド。
【請求項２６】 脈管形成環境においてポリペプチドの発現がダウンレギュレートされ、ポリペプチドがＰＡ：５、１４及び１５からなる群から選択される請求項２５に記載のポリペプチド。
【請求項２７】 脈管形成環境においてポリペプチドの発現がアップレギュレートされ、ポリペプチドがＰＡ：１−４、６−１３及び１６−２６からなる群から選択される請求項２５に記載のポリペプチド。
【請求項２８】 被検体が哺乳動物である請求項２５に記載のポリペプチド。
【請求項２９】 被検体がヒトである請求項２８に記載のポリペプチド。
【請求項３０】 被検体における脈管形成障害を治療するために使用される単離された核酸分子であって、ＰＡ：１−２７の核酸配列又はその核酸配列の相補鎖の何れか１つと少なくとも７５％同一の核酸分子。
【請求項３１】 脈管形成環境において核酸配列の発現状態がダウンレギュレートされ、核酸がＰＡ：５、１４及び１５からなる群から選択される請求項３０に記載の核酸分子。
【請求項３２】 脈管形成環境において核酸配列の発現状態がアップレギュレートされ、核酸がＰＡ：１−４、６−１３及び１６−２６からなる群から選択される請求項３０に記載の核酸分子。
【請求項３３】 被検体が哺乳動物である請求項３０に記載の核酸分子。
【請求項３４】 被検体がヒトである請求項３３に記載の核酸分子。
【請求項３５】 請求項２５に記載のポリペプチドと、製薬的に許容可能な担体とを含んでなる治療用組成物。
【請求項３６】 心血管作動薬、内皮薬、脈管形成薬、及び血管拡張薬からなる群から選択される付加的活性成分をさらに含む請求項３５に記載の治療用組成物。
【請求項３７】 請求項３０に記載の核酸分子と、製薬的に許容可能な担体とを含んでなる治療用組成物。
【請求項３８】 心血管作動薬、内皮薬、脈管形成薬、及び血管拡張薬からなる群から選択される付加的活性成分をさらに含む請求項３７に記載の治療用組成物。
【請求項３９】 ＰＡポリペプチドのアゴニスト又はアンタゴニストと、製薬的に許容可能な担体とを含んでなる治療用組成物。
【請求項４０】 心血管作動薬、内皮薬、脈管形成薬、及び血管拡張薬からなる群から選択される付加的活性成分をさらに含む請求項３９に記載の治療用組成物。
【請求項４１】 脈管形成障害の治療において用いられる治療用組成物と、製薬的に許容可能な担体とを含んでなるキットであって、前記治療用組成物が、ＰＡポリペプチド、ＰＡポリペプチドのアゴニスト、及びＰＡポリペプチドのアンタゴニストからなる群から選択されるキット。
【請求項４２】 請求項３５に記載の治療用組成物を含有してなる脈管形成障害の治療のための医薬。
【請求項４３】 請求項３７に記載の治療用組成物を含有してなる脈管形成障害の治療のための医薬。
【請求項４４】 哺乳動物における脈管形成を阻害するための薬剤であって、ＰＡポリペプチド、ＰＡポリペプチドのアゴニスト、ＰＡポリペプチドのアンタゴニスト、及び抗ＰＡ抗体からなる群から選択される脈管形成を阻害する治療用組成物の治療的有効量を含有してなる薬剤。
【請求項４５】 哺乳動物における脈管形成を刺激するための薬剤であって、ＰＡポリペプチド、ＰＡポリペプチドのアゴニスト、ＰＡポリペプチドのアンタゴニスト、及び抗ＰＡ抗体からなる群から選択される脈管形成を刺激する治療用組成物の治療的有効量を含有してなる薬剤。
【請求項４６】 配列番号：７２のポリペプチドをコードする核酸配列、又はその核酸配列の相補鎖と少なくとも７５％同一である核酸配列を含む単離された核酸分子。
【請求項４７】 請求項４６に記載の核酸配列を含む核酸ベクター。
【請求項４８】 請求項４６に記載の単離された核酸分子を含む宿主細胞。
【請求項４９】 ａ）配列番号：７２のアミノ酸配列を含むポリペプチド；
ｂ）配列番号：７２のアミノ酸配列を含むポリペプチドの断片であって、少なくとも６の連続するアミノ酸を含む断片；
ｃ）配列番号：７２のアミノ酸配列を含むポリペプチドの誘導体；
ｄ）配列番号：７２のアミノ酸配列を含むポリペプチドの類似物；及び
ｅ）配列番号：７２のアミノ酸配列を含むポリペプチドの相同体
からなる群から選択されるポリペプチドと少なくとも８０％同一の単離されたポリペプチド。
【請求項５０】 請求項４９に記載のポリペプチドに選択的に結合する抗体、又は該抗体の断片、相同体、類似物ないしは誘導体。
【請求項５１】 請求項４６に記載の核酸を含んでなる医薬組成物。
【請求項５２】 請求項４９に記載のポリペプチドを含んでなる医薬組成物。
【請求項５３】 試料中の請求項４６に記載の核酸の存在を検出する方法であって、試料を請求項４６に記載の核酸に選択的に結合する化合物と接触させ、請求項４６に記載の核酸に結合した化合物が試料中に存在するか否かを決定することを含む方法。
【請求項５４】 試料中の請求項４９に記載のポリペプチドの存在を検出する方法であって、試料を請求項４９に記載のポリペプチドに選択的に結合する化合物と接触させ、請求項４９に記載のポリペプチドに結合した化合物が試料中に存在するか否かを決定することを含む方法。
[Claims]
(1) SubjectA method for evaluating the effectiveness of an angiogenesis disorder treatment in a subject,
a)Selected from the group consisting of PA: 1-27 in the test cell populationDetecting the expression of one or more nucleic acid sequences,
bC.) Comparing the expression of the nucleic acid sequence in the test cell population with the expression of the nucleic acid sequence in a reference cell population comprising at least one cell of known angiogenic stage;
c)) Identify the differences in the expression levels of the PA: 1-27 sequence, if present, in the test and reference cell populations,SubjectAssessing the effectiveness of a treatment for an angiogenic disorder in a subject.
(2) SubjectDiagnosis of Angiogenesis Disorder in ChildrenOr determine susceptibility to angiogenic disordersIn the method,
a)Selected from the group consisting of PA: 1-27 in the test cell populationDetecting the expression of one or more nucleic acid sequences,
bC.) Comparing the expression of the nucleic acid sequence in the test cell population with the expression of the nucleic acid sequence in a reference cell population comprising at least one cell of known angiogenic stage;
c)) Identify the differences in the expression levels of the PA: 1-27 sequence, if present, in the test and reference cell populations,SubjectDiagnosis of angiogenesis disorders in childrenOr determine susceptibility to angiogenic disordersA method that includes:
(3) SubjectA method of identifying a test therapeutic for treating an angiogenic disorder in a subject,
a)PA: one or more nucleic acid sequences of the group consisting of 1-27 can be expressedContacting a test cell population with a test therapeutic;
b)Contacted with study treatmentDetecting expression of one or more nucleic acid sequences in said test cell population;
cC.) Comparing the expression of the nucleic acid sequence in the test cell population with the expression of the nucleic acid sequence in a reference cell population comprising at least one cell of known angiogenic stage;
d) If present,Contacted with study treatmentIdentifying differences in the expression levels of the PA: 1-27 sequence in the test and reference cell populations, therebySubjectIdentifying a test therapeutic for the treatment of an angiogenic disorder of the subject.
4. The method of claim 1, wherein the test drug is a known anti-angiogenic disorder drug.3The method described in.
5. The method of claim 1, wherein the test therapeutic is an agonist of the natural PA polypeptide.3The method described in.
6. The method of claim 6, wherein the test therapeutic is an antagonist of the natural PA polypeptide.3The method described in.
7. The method according to claim 7, wherein the agonist is an anti-PA antibody.5The method described in.
8. The method according to claim 8, wherein the antagonist is an anti-PA antibody.6The method described in.
9. The method of claim 1, wherein the test drug is an unknown anti-angiogenesis disorder.3The method described in.
10. The angiogenesis disorder is a vascular tumor, proliferative vitreoretinopathy, rheumatoid arthritis, Crohn's disease, atherosclerosis, ovarian hyperstimulation, psoriasis, endometriosis with neovascularization, Restenosis following balloon angioplasty, hyperplasia of scar tissue, peripheral vasculopathy, hypertension, inflammatory vasculitis, Reynolds disease and Reynolds phenomenon, aneurysm, arterial restenosis, thrombophlebitis, lymphangitis Claims selected from the group consisting of: lymphedema, wound healing and tissue regeneration, ischemic reperfusion injury, angina, myocardial infarction, chronic heart abnormalities, heart failure such as congestive heart failure, age-related macular degeneration, and osteoporosis.Any one of 1 to 9The method described in.
11. The method according to any one of claims 1 to 9, wherein the angiogenesis disorder is a cancer selected from the group consisting of breast cancer, renal cell epithelial cancer, squamous cell carcinoma, colorectal epithelial cancer and prostate epithelial cancer.
12. The method of claim 1, wherein the expression of the nucleic acid sequence in the test cell population is increased as compared to the reference cell population.Any one of 3The method described in.
13. The method of claim 1, wherein the expression of the nucleic acid sequence in the test cell population is reduced as compared to the reference cell population.Any one of 3The method described in.
14. The method of claim 1, wherein the test cell population is provided in vitro.Any one of 5The method described in.
15. The test cell population is a mammalSubjectAnd supplied ex vivo fromAny one of 5The method described in.
16. SubjectIs a mammalAny one of 1 to 15The method described in.
17. SubjectIs a human16The method described in.
18. Of patients suffering from or at risk of developing an angiogenic disorderTreatment of angiogenic disordersMedicine forAn agent that modulates the expression or activity of one or more nucleic acid sequences selected from the group consisting of PA: 1-27Pharmaceutical containing.
(19) The drug, PA: decrease the expression or activity of one or more nucleic acid sequences selected from the group consisting of 5, 14, and 15ContractRequest18Described inMedicine.
20. The drug, PA: increase the expression or activity of one or more nucleic acid sequences selected from the group consisting of: 1-4, 6-13 and 16-26ContractRequest18Described inMedicine.
21. The agent is an antibody against a polypeptide encoded by the PA nucleic acid sequence, an antisense nucleic acid molecule, a peptide, a PA polypeptide agonist, a PA polypeptide antagonist, a peptide analog, a small molecule, or another drug. Claim18Described inMedicine.
22. The angiogenesis disorder is selected from the group consisting of cardiac hypertrophy, trauma, age-related macular degeneration, and cancer.18Described inMedicine.
23. A kit comprising one or more reagents for detecting two or more nucleic acid sequences selected from the group consisting of PA: 1-27.
24. An array of probe nucleic acids, wherein said probe nucleic acids detect two or more nucleic acid sequences selected from the group consisting of PA: 1-27.
25. SubjectAn isolated polypeptide for use in treating an angiogenic disorder in
a) PA: a polypeptide comprising the amino acid sequence of 1-27;
b) a fragment of a polypeptide comprising the amino acid sequence of PA: 1-27, wherein the fragment comprises at least 6 consecutive amino acids of PA: 1-27;
c) PA: a derivative of a polypeptide comprising the amino acid sequence of 1-27;
d) PA: analogs of a polypeptide comprising the amino acid sequence of 1-27; and
e) PA: homolog of polypeptide comprising amino acid sequence of 1-27
A polypeptide that is at least 80% identical to a polypeptide selected from the group consisting of:
26. The method according to claim 26, wherein the expression of the polypeptide is down-regulated in the angiogenic environment, and the polypeptide is selected from the group consisting of PA: 5, 14 and 15.252. The polypeptide according to item 1.
27. The expression of the polypeptide is up-regulated in an angiogenic environment, and the polypeptide is selected from the group consisting of PA: 1-4, 6-13 and 16-26.252. The polypeptide according to item 1.
28. SubjectIs a mammal252. The polypeptide according to item 1.
29. SubjectIs a human282. The polypeptide according to item 1.
30. SubjectCLAIMS 1. An isolated nucleic acid molecule for use in treating an angiogenic disorder in a subject, comprising the nucleic acid sequence of PA: 1-27 or the complement of the nucleic acid sequence.Any of the chainsA nucleic acid molecule that is at least 75% identical to one.
31. The nucleic acid sequence is downregulated in an angiogenic environment and the nucleic acid is selected from the group consisting of PA: 5, 14, and 15.303. The nucleic acid molecule according to claim 1.
32. The expression status of a nucleic acid sequence is up-regulated in an angiogenic environment, and the nucleic acid is selected from the group consisting of PA: 1-4, 6-13 and 16-26.303. The nucleic acid molecule according to claim 1.
33. SubjectIs a mammal303. The nucleic acid molecule according to claim 1.
34. SubjectIs a human333. The nucleic acid molecule according to claim 1.
Claim 3525A therapeutic composition comprising the polypeptide of claim 1 and a pharmaceutically acceptable carrier.
36. The method according to claim 36, further comprising an additional active ingredient selected from the group consisting of cardiovascular drugs, endothelial drugs, angiogenic drugs, and vasodilators.353. The therapeutic composition according to item 1.
37. Claim30A therapeutic composition comprising the nucleic acid molecule of claim 1 and a pharmaceutically acceptable carrier.
38. The method according to claim 18, further comprising an additional active ingredient selected from the group consisting of cardiovascular drugs, endothelial drugs, angiogenic drugs, and vasodilators.373. The therapeutic composition according to item 1.
39. A therapeutic composition comprising an agonist or antagonist of a PA polypeptide and a pharmaceutically acceptable carrier.
40. The method further comprising an additional active ingredient selected from the group consisting of cardiovascular drugs, endothelial drugs, angiogenic drugs, and vasodilators.393. The therapeutic composition according to item 1.
41. A kit comprising a therapeutic composition for use in the treatment of an angiogenic disorder, and a pharmaceutically acceptable carrier, wherein the therapeutic composition comprises a PA polypeptide, a PA polypeptide. A kit selected from the group consisting of a peptide agonist and a PA polypeptide antagonist.
Claim 4235The therapeutic composition according toContainTreatment of angiogenic disordersMedicine for.
Claim 4337The therapeutic composition according toContainTreatment of angiogenic disordersMedicine for.
44. Inhibition of angiogenesis in a mammalDrugs forAndSelected from the group consisting of PA polypeptides, PA polypeptide agonists, PA polypeptide antagonists, and anti-PA antibodiesA therapeutically effective amount of a therapeutic composition that inhibits angiogenesis.Drugs contained.
45. Stimulates angiogenesis in a mammalDrugs forAndSelected from the group consisting of PA polypeptides, PA polypeptide agonists, PA polypeptide antagonists, and anti-PA antibodiesA therapeutically effective amount of a therapeutic composition that stimulates angiogenesis.Drugs contained.
46. A nucleic acid sequence encoding the polypeptide of SEQ ID NO: 72, or the complement of the nucleic acid sequencechainAn isolated nucleic acid molecule comprising a nucleic acid sequence that is at least 75% identical to a nucleic acid sequence.
Claim 4746A nucleic acid vector comprising the nucleic acid sequence according to 1.
Claim 4846A host cell comprising the isolated nucleic acid molecule of claim 1.
49) a) a polypeptide comprising the amino acid sequence of SEQ ID NO: 72;
b) a fragment of a polypeptide comprising the amino acid sequence of SEQ ID NO: 72, wherein the fragment comprises at least 6 consecutive amino acids;
c) a derivative of a polypeptide comprising the amino acid sequence of SEQ ID NO: 72;
d) analogs of a polypeptide comprising the amino acid sequence of SEQ ID NO: 72;
e) homologue of a polypeptide comprising the amino acid sequence of SEQ ID NO: 72
An isolated polypeptide at least 80% identical to a polypeptide selected from the group consisting of:
50. 50. An antibody that selectively binds to the polypeptide of claim 49, or a fragment, homolog, analog or derivative of said antibody..
Claim 5146A pharmaceutical composition comprising the nucleic acid according to item 1.
52. Claim49A pharmaceutical composition comprising the polypeptide according to item 1.
53. The claim in the sample46A method for detecting the presence of a nucleic acid according to claim 1, wherein the sample is46Contacting with a compound that selectively binds to the nucleic acid according to claim.46Whether the compound bound to the nucleic acid described in the above is present in the sample.DecisionA method that includes doing.
54. The claim in the sample49A method for detecting the presence of a polypeptide according to claim 1, wherein the sample is49Contacting with a compound that selectively binds to the polypeptide of claim.49Whether the compound bound to the polypeptide described in the above is present in the sample.DecisionA method that includes doing.
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US16269999P | 1999-11-01 | 1999-11-01 | |
| US60/162,699 | 1999-11-01 | ||
| US19680200P | 2000-04-13 | 2000-04-13 | |
| US60/196,802 | 2000-04-13 | ||
| US70335000A | 2000-10-31 | 2000-10-31 | |
| US09/703,350 | 2000-10-31 | ||
| PCT/US2000/030051 WO2001032926A2 (en) | 1999-11-01 | 2000-11-01 | Differentially expressed genes involved in angiogenesis, the polypeptides encoded thereby, and methods of using the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2003525595A JP2003525595A (en) | 2003-09-02 |
| JP2003525595A5 true JP2003525595A5 (en) | 2007-12-20 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2001535606A Pending JP2003525595A (en) | 1999-11-01 | 2000-11-01 | Differentially expressed gene involved in angiogenesis, polypeptide encoded thereby, and method using the same |
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| JP (1) | JP2003525595A (en) |
| AU (2) | AU784338B2 (en) |
| CA (1) | CA2389751A1 (en) |
| WO (1) | WO2001032926A2 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7994159B2 (en) | 2003-03-10 | 2011-08-09 | Eisai R&D Management Co., Ltd. | c-Kit kinase inhibitor |
| US8952035B2 (en) | 2007-11-09 | 2015-02-10 | Eisai R&D Management Co., Ltd. | Combination of anti-angiogenic substance and anti-tumor platinum complex |
| US8969344B2 (en) | 2005-08-02 | 2015-03-03 | Eisai R&D Management Co., Ltd. | Method for assay on the effect of vascularization inhibitor |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2798674B1 (en) * | 1999-09-21 | 2004-01-30 | Mahmood Salman Al | METHOD FOR IDENTIFYING NEW GENES INVOLVED IN THE REGULATION OF ANGIOGENESIS, STUDY OF THESE GENES AND THEIR USE FOR THERAPEUTIC PURPOSES |
| HU230302B1 (en) | 2000-10-20 | 2015-12-28 | Eisai R&D Management Co., Ltd. | Nitrogenous aromatic ring compounds and pharmaceutical compositions containing them |
| CA2461372C (en) * | 2001-09-27 | 2014-01-07 | Bionomics Limited | Dna sequences for human angiogenesis genes |
| WO2004039955A2 (en) * | 2002-10-29 | 2004-05-13 | Rigel Pharmaceuticals, Inc. | Modulators of angiogenesis and tumorigenesis |
| US7407660B2 (en) | 2003-04-16 | 2008-08-05 | Genentech, Inc. | Methods and compositions for selective modulation of vascularization |
| EP1664787A1 (en) * | 2003-08-08 | 2006-06-07 | Roche Diagnostics GmbH | Use of protein t-plastin (plst) as a marker for colorectal cancer |
| WO2005015227A1 (en) * | 2003-08-08 | 2005-02-17 | Roche Diagnostics Gmbh | Use of protein t- plastin (plst) as a marker for colorectal cancer |
| CN100450998C (en) | 2003-11-11 | 2009-01-14 | 卫材R&D管理有限公司 | Process for the preparation of urea derivatives |
| EP1721158A4 (en) * | 2004-01-13 | 2008-07-30 | Rigel Pharmaceuticals Inc | Modulators of angiogenesis |
| EP1797881B1 (en) | 2004-09-17 | 2009-04-15 | Eisai R&D Management Co., Ltd. | Medicinal composition with improved stability and reduced gelation properties |
| JP2006333770A (en) * | 2005-06-01 | 2006-12-14 | Japan Science & Technology Agency | Blood cell-specific genes in patients with angiitis |
| WO2007022625A1 (en) * | 2005-08-22 | 2007-03-01 | Caprion Pharmaceuticals Inc. | Peptide reversion methods and uses thereof |
| CN101316590B (en) | 2005-11-07 | 2011-08-03 | 卫材R&D管理有限公司 | combined use of angiogenesis inhibitor and c-kit kinase inhibitor |
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| CA3057748A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
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Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1993023075A1 (en) * | 1992-05-14 | 1993-11-25 | Oncologix, Inc. | Treatment of vascular leakage syndrome and collagenase induced disease by administration of matrix metalloproteinase inhibitors |
| JP2001521365A (en) * | 1996-02-16 | 2001-11-06 | ミレニウム ファーマシューティカルズ，インコーポレーテッド | Compositions and methods for treatment and diagnosis of cardiovascular disease |
| DE19701607A1 (en) * | 1997-01-17 | 1998-07-23 | Hoechst Ag | Antibodies that bind to the nidogen-binding domain of laminin, their production and use |
| EP1070727A1 (en) * | 1999-03-01 | 2001-01-24 | Aventis Pharma Deutschland GmbH | Low molecular weight peptide derivatives as inhibitors of the laminin/nidogen interaction |
| AU3395900A (en) * | 1999-03-12 | 2000-10-04 | Human Genome Sciences, Inc. | Human lung cancer associated gene sequences and polypeptides |
| CA2387685A1 (en) | 1999-10-27 | 2001-05-03 | Human Genome Sciences, Inc. | Stanniocalcin proteins and nucleic acids and methods based thereon |
| CA2403515A1 (en) * | 2000-03-29 | 2001-10-04 | Beth Israel Deaconess Medical Center, Inc. | Anti-angiogenic and anti-tumor properties of vascostatin and other nidogen domains |
-
2000
- 2000-11-01 WO PCT/US2000/030051 patent/WO2001032926A2/en not_active Ceased
- 2000-11-01 CA CA002389751A patent/CA2389751A1/en not_active Abandoned
- 2000-11-01 JP JP2001535606A patent/JP2003525595A/en active Pending
- 2000-11-01 AU AU14493/01A patent/AU784338B2/en not_active Ceased
-
2006
- 2006-06-16 AU AU2006202570A patent/AU2006202570A1/en not_active Abandoned
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7994159B2 (en) | 2003-03-10 | 2011-08-09 | Eisai R&D Management Co., Ltd. | c-Kit kinase inhibitor |
| US8969344B2 (en) | 2005-08-02 | 2015-03-03 | Eisai R&D Management Co., Ltd. | Method for assay on the effect of vascularization inhibitor |
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