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-047/48
A61K-051/08
C07K-007/08
C07K-014/52
C07K-014/71
A61K-038/00
출원번호
US-0019241
(2013-09-05)
등록번호
US-9629934
(2017-04-25)
발명자
/ 주소
Sato, Aaron K.
Sexton, Daniel J.
Dransfield, Daniel T.
Ladner, Robert Charles
출원인 / 주소
Dyax Corp.
대리인 / 주소
Wolf, Greenfield & Sacks, P.C.
인용정보
피인용 횟수 :
0인용 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. A method for treating an ocular disease that involves angiogenesis, comprising administering to a subject in need thereof an effective amount of a VEGF/KDR-binding peptide, which comprises a motif of: (i) Cys-X2-X3-X4-X5-X6-Tyr-Cys, wherein X2 is Ala, Arg, Glu, Lys, or Ser; X3 is Ala, Asp, Gln, G
1. A method for treating an ocular disease that involves angiogenesis, comprising administering to a subject in need thereof an effective amount of a VEGF/KDR-binding peptide, which comprises a motif of: (i) Cys-X2-X3-X4-X5-X6-Tyr-Cys, wherein X2 is Ala, Arg, Glu, Lys, or Ser; X3 is Ala, Asp, Gln, Glu, Thr, or Val; X4 is Asp or Glu; X5 is Trp or Tyr; and X6 is Thr or Tyr; or(ii) Cys-X2-X3-X4-X5-Trp-Gly-Gly-X9-X10-Cys (SEQ ID NO:14), wherein X2 is Ala, Phe, or Trp; X3 is Glu or Lys; X4 is Asp, Ser, Trp, or Tyr; X5 is Phe, Pro, or Ser, X9 is Gln or Glu; and X10 is Ile, Phe, or Val; wherein the VEGF/KDR-binding peptide is either monomeric or homomultimeric. 2. The method of claim 1, wherein the ocular disease is selected from the group consisting of diabetic retinopathy, retinopathy of prematurity, macular degeneration, and corneal graft rejection. 3. The method of claim 1, wherein the peptide has fewer than 25 amino acids. 4. The method of claim 1, wherein the peptide comprises Cys-X2-X3-X4-X5-X6-Tyr-Cys, in which X2 is Glu; X3 is Asp or Glu; X4 is Asp or Glu; X5 is Trp or Tyr; and X6 is Tyr. 5. The method of claim 4, wherein the peptide comprises an amino acid sequence selected from the group consisting of: (a)AGPTWCEDDWYYCWLFGTK,(SEQ ID NO: 493)(b)AGPTWCEDDWYYCWLFGTGGGK,(SEQ ID NO: 277)(c)AGPTWCEDDWYYCWLFGTGGGGK,(SEQ ID NO: 480)(d)AGPTWCEDDWYYCWLFGTGGGKK,(SEQ ID NO: 373) and (e) a variant thereof that includes a truncation of one or more residues at the C-terminus or the N-terminus. 6. The method of claim 1, wherein the peptide comprises Cys-X2-X3-X4-X5-Trp-Gly-Gly-X9-X10-Cys (SEQ ID NO:14), in which X2 is Phe or Trp; X3 is Glu; X4 is Asp, Trp, or Tyr; X5 is Ser, X9 is Glu; and X10 is Ile, Phe, or Val. 7. The method of claim 6, wherein the peptide comprises an amino acid sequence selected from the group consisting of: (iii)GDSRVCWEDSWGGEVCFRYDP,(SEQ ID NO: 374)(iv)GDSRVCWEDSWGGEVCFRYDPGGGK,(SEQ ID NO: 294)and(v)GDSRVCWEDSWGGEVCFRYGGGK.(SEQ ID NO: 372) 8. The method of claim 1, wherein the peptide is modified. 9. The method of claim 8, wherein the peptide is modified at the N-terminus, the C-terminus, or both. 10. The method of claim 9, wherein the peptide has an acetylated N-terminus, an amidated C-terminus, or both. 11. The method of claim 1, wherein the VEGF/KDR-binding peptide is in a dimeric construct containing two copies of the same VEGF/KDR-binding peptide. 12. The method of claim 1, wherein the peptide is conjugated with a therapeutic agent. 13. The method of claim 1, wherein the therapeutic agent is an antibody or a fragment thereof. 14. The method of claim 12, wherein the peptide and the therapeutic agent is connected via a spacer. 15. The method of claim 14, wherein the spacer is a substituted or unsubstituted alkyl chain, a polyethylene glycol derivative, an amino acid spacer, a sugar spacer, or an aromatic spacer.
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