Methods of modulating of angiogenesis

• US 6,395,548 B1
• Filed: 08/13/1999
• Issued: 05/28/2002
• Est. Priority Date: 08/14/1998
• Status: Expired due to Fees

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Maemura, Koji, Hsieh, Chung-Ming, Lee, Mu-En
• Primary Examiner(s): Nguyen, Dave T.
• Assistant Examiner(s): Shukla, Ram R.
• Application Number:
  US09/374,454
• Time in Patent Office: 1,019 Days
• Field of Search: 514/44,2 435/455,320.1,325 536/23.1,23.5,24.1,24.2,24.5
• US Class Current: 435/455
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: G06F 16/289 Object oriented databases

Abstract

A method of inhibiting angiogenesis in a mammal by administering to the mammal a compound which inhibits binding of endothelial PAS domain protein-1 to cis-acting transcription regulatory sequence in the promoter region of a gene encoding an angiogenic factor.

Claims

1. A nucleic acid encoding a deletion mutant of an EPAS1 polypeptide which deletion mutant binds to the nucleotide sequence of SEQ ID NO:

1, wherein said EPAS1 polypeptide consists of the amino acid sequence of SEQ ID NO;

6 and wherein said deletion mutant comprises the amino acid sequence of SEQ ID NO;

4 and a functional deletion in a transactivation domain, said transactivation domain consisting of the amino acid sequence of SEQ ID NO;

2.

2. The nucleic acid of claim 1, wherein said nucleic acid encodes an EPAS1 polypeptide lacking amino acids 486-639 of SEQ ID NO:

6.

3. The nucleic acid of claim 1, wherein said EPAS1 polypeptide comprises the amino acid sequence of SEQ ID NO:

4.

4. The nucleic acid of claim 1 wherein said nucleic acid comprises the nucleotide sequence of SEQ ID NO:

5.

5. A method of inhibiting expression of an angiogenic factor in a mammalian vascular endothelial cell in vitro, comprising contacting said mammalian vascular endotheliar cell with the nucleic acid of claim 1, wherein the promoter of said angiogenic factor comprises the nucleotide sequence disclosed in SEQ ID NO1.

6. The method of claim 5, wherein said nucleic acid encodes an EPAS1 polypeptide comprising the amino acid sequence of SEQ ID NO:

4.

7. The method of claim 5, wherein said nucleic acid comprises the nucleotide sequence of SEQ ID NO:

5.