Peptide and polypeptide inhibitors of complement C1s

• US 7,071,299 B2
• Filed: 06/18/2001
• Issued: 07/04/2006
• Est. Priority Date: 06/21/2000
• Status: Expired due to Fees

• Current Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Original Assignee: Zymogenetics Incorporated (Bristol-Myers Squibb Company)
• Inventors: Sheppard, Paul O., Fox, Brian A., West, Robert R.
• Primary Examiner(s): Chan, Christina
• Assistant Examiner(s): VANDERVEGT, FRANCOIS P
• Application Number:
  US09/883,727
• Publication Number:
  US 20020102256A1
• Time in Patent Office: 1,842 Days
• Field of Search: 530/325, 530/324, 530/326, 530/327, 530/328, 530/329, 530/330, 424/184.1, 424/485.1, 424/278.1
• US Class Current: 530/324
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: C07K 14/43536 from worms
• CPC Class Codes: C07K 14/815 from leeches, e.g. hirudin, eglin

Abstract

The complement system plays an important role in providing resistance to infections and in the pathogenesis of tissue injury. Yet an inappropriate activation of complement can result in a variety of disorders. The present invention provides C1s catalytic site-directed moieties, C1s exosite binding moieties, and bivalent polypeptide inhibitors comprising such moieties, which can be used to treat conditions characterized by inappropriate complement activation.

Claims

1. A peptide or polypeptide that inhibits complement C1s, wherein the peptide or polypeptide comprises the amino acid sequence “

CRLGC”

(amino acid residues 64 to 68 of SEQ ID NO;

1), wherein the peptide or polypeptide consists of five to thirty amino acid residues of SEQ ID NO;

1.

2. The peptide or polypeptide of claim 1, wherein the polypeptide consists of the amino acid sequence:

3. The peptide or polypeptide of claim 1, wherein the peptide consists of the amino acid sequence:

“

CRLGC”

(amino acid residues 64 to 68 of SEQ ID NO;

1).