Peptides and compounds that bind to the IL-1 receptor

• US 5,880,096 A
• Filed: 06/05/1995
• Issued: 03/09/1999
• Est. Priority Date: 02/02/1994
• Status: Expired due to Fees

• Current Assignee: Affymax Incorporated
• Original Assignee: Affymax Incorporated
• Inventors: Barrett, Ronald W., Yanofsky, Stephen D.
• Primary Examiner(s): Hutzell, Paula K.
• Assistant Examiner(s): DUFFY, PATRICIA ANN
• Application Number:
  US08/463,076
• Time in Patent Office: 1,373 Days
• Field of Search: 514/12, 514/2, 514/13, 514/14, 514/15, 424/85.2, 424/1.41, 530/327, 530/345
• US Class Current: 514/20.6
• 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 14/545 IL-1

Abstract

Peptides that bind to the interleukin-1 type I receptor (IL-1RtI) can be used to assay the amount of IL-1R, or an IL-1R agonist or antagonist, in a sample and comprise a sequence of amino acids selected from the group consisting of (1) WXXXGZ₁ W where Z₁ is L, I, A, or Q (SEQ ID NO:2); (2) XXQZ₅ YZ₆ XX where Z₅ is P or Aze where Aze is azetidine; and Z₆ is S, A, V, or L (SEQ ID NO:1); and (3) Z₂₃ NZ₂₄ SZ₂₅ Z₂₆ Z₂₇ Z₂₈ Z₂₉ Z₃₀ L where Z₂₃ is D or Y; Z₂₄ is D or S; Z₂₅ is S or W; Z₂₆ is S or Y; Z₂₇ is D or V; Z₂₈ is S or W; Z₂₉ is F or L; and Z₃₀ is D or L (SEQ ID NO:27); and where each amino acid is indicated by standard one letter abbreviation; and each X can be selected from any one of the 20 genetically coded L-amino acids or the stereoisomeric D-amino acids. Also provided are peptides which bind to the IL-1RtI, which are 11 to 40 amino acids in length, which comprise the core sequence of amino acids:

Z.sub.31 XWZ.sub.32 Z.sub.33 Z.sub.34 Z.sub.35 Z.sub.36 QZ.sub.37 Z.sub.38

where each letter represents the standard one letter abbreviation for an amino acid or an analog thereof; X is selected from the group of natural or unnatural amino acids; Z₃₇ is a natural or unnatural cyclic amino acid; Z₃₁ is selected from phenylalanine and acetylated phenylalanine; Z₃₂ is a natural or unnatural amino acid; Z₃₃ is selected from proline and pipecolic acid; Z₃₄ is selected from glycine, d-alanine, d-valine, sarcosine and aminoisobutyric acid; Z₃₅ is a natural or unnatural amino acid and Z₃₆ is selected from tyrosine, phosphotyrosine, phenylalanine and tryptophan; and Z₃₈ is selected from tyrosinamide and substituted tyrosinamide (SEQ ID NO:392).

Claims

1. A compound of 11 to 40 amino acids in length that binds to an interleukin-1 type I receptor and comprises the sequence

View Dependent Claims (2, 3, 4, 5)

2. The compound of claim 1, further comprising a cytotoxic agent conjugated thereto.

3. A pharmaceutical composition, comprising the compound of claim 1 in combination with a pharmaceutically acceptable carrier.

4. The compound of claim 1, wherein the sequence

5. The compound of claim 1, wherein said compound is selected from the group consisting of DNSSWYDSFLL (SEQ ID NO:

370);

DNTAWYESFLA (SEQ ID NO;

371);

DNTAWYENFLL (SEQ ID NO;

372);

PAREDNTAWYDSFLIWC (SEQ ID NO;

374);

TSEYDNTTWYEKFLASQ (SEQ ID NO;

375);

SQIPDNTAWYSFLLHG (SEQ ID NO;

376);

SPFIDNTAWYENFLLTY (SEQ ID NO;

377);

EQIYDNTAWYDHFLLSY (SEQ ID NO;

378);

TPFIDNTAWYENFLLTY (SEQ ID NO;

379);

TYTYDNTAWYERFLMSY (SEQ ID NO;

380);

TMTQDNTAWYENFLLSY (SEQ ID NO;

381);

TIDNTAWYANLVQTYPQ (SEQ ID NO;

383);

TIDNTAWYERFLAQYPD (SEQ ID NO;

384);

HIDNTAWYENFLLTYTP (SEQ ID NO;

385);

SQDNTAWYENFLLSYKA (SEQ ID NO;

386);

QIDNTAWYERFLLQYNA (SEQ ID NO;

387);

NQDNTAWYESFLLQYNT (SEQ ID NO;

388);

TIDNTAWYENFLLNHNL (SEQ ID NO;

389); and

HYDNTAWYERFLQQGWY (SEQ ID NO;

390).