Multifunctional polypeptides

• US 20030049689A1
• Filed: 06/12/2002
• Published: 03/13/2003
• Est. Priority Date: 12/14/2000
• Status: Abandoned Application

• Current Assignee: Genencor International Incorporated (International Flavors & Fragrances Incorporated)
• Original Assignee: Genencor International Incorporated (International Flavors & Fragrances Incorporated)
• Inventors: Edwards, Cynthia, Schellenberger, Volker, Day, Anthony G., Murray, Christopher J., Chen, Yiyou
• Application Number:
  US10/170,729
• Publication Number:
  US 20030049689A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• 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: A61K 47/6415 Toxins or lectins, e.g. clostridial toxins or Pseudomonas exotoxins
• CPC Class Codes: A61K 47/67 Enzyme prodrug therapy, e.g. gene directed enzyme drug therapy [GDEPT] or VDEPT
• CPC Class Codes: A61K 47/6891 Pre-targeting systems involving an antibody for targeting specific cells
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 2319/00 Fusion polypeptide
• CPC Class Codes: C07K 2319/50 containing protease site
• CPC Class Codes: C07K 2319/55 containing a fusion with a toxin, e.g. diphteria toxin
• CPC Class Codes: C07K 2319/70 containing domain for protein-protein interaction
• CPC Class Codes: C12N 15/1044 Preparation or screening of libraries displayed on scaffold proteins
• CPC Class Codes: C12N 15/62 DNA sequences coding for fusion proteins
• CPC Class Codes: C12N 9/50 Proteinases , e.g. Endopeptidases (3.4.21-3.4.25)
• CPC Class Codes: C12N 9/64 derived from animal tissue
• CPC Class Codes: C12N 9/86 acting on amide bonds in cyclic amides, e.g. penicillinase (3.5.2)

Abstract

The present invention provides methods and compositions relating to polypeptides engineered to bind a target and have at least two functional domains.

Claims

1. ) A method of making a multifunctional polypeptide comprising

a) selecting from a library of peptides a peptide that binds to a target, and

b) making a multifunctional polypeptide that comprises the sequence of said peptide selected in step (a) and at least two functional domains.

2. ) The method of claim 1 wherein the target comprises a molecule or surface associated with a tissue, an organ or a cell.

3. ) The method of claim 2 wherein the tissue, organ or cell is diseased, injured, infected, cancerous, healthy or normal.

4. ) A method of selectively targeting a target comprising contacting said target with a multifunctional polypeptide wherein said multifunctional polypeptide comprises a first low affinity targeted peptide for a first microtarget and a second low affinity targeted peptide for a second microtarget, said target comprises said first and said second microtargets, and a non-target does not comprise both said first and said second microtargets, such that the affinity and specificity of said multifunctional polypeptide is higher for said target than it is for said non-target.

5. ) The method of claim 4 wherein the multifunctional polypeptide is administered to a subject and said subject comprises said target and said non-target.

6. ) The method of claim 5 wherein the target is a diseased, injured or infected tissue, organ or cell.

7. ) The method of claim 6 wherein the target is a cancerous tissue, organ cell or tumor.

8. ) The method of claim 7 wherein the first microtarget is p97.

9. ) The method of claim 5 wherein the non-target is a normal or healthy tissue, organ or cell.

11. ) The method of claim 5 wherein the multifunctional polypeptide further comprises a functional domain.

12. ) The method of claim 11 wherein the functional domain is a diagnostic or therapeutic functional domain.

13. ) The method of claim 12 wherein the target is a tissue, organ or cell and the therapeutic functional domain is toxic to the target tissue, organ or cell.

14. ) The method of claim 12 wherein the target is a tissue, organ or cell and the therapeutic functional domain stimulates the target tissue, organ or cell.

15. ) The method of claim 4 wherein the multifunctional polypeptide further comprises a functional domain.

16. ) A method of killing a tissue, organ or cell in a subject comprising administering to said subject a multifunctional polypeptide comprising a targeting domain, a first cytotoxic domain and a second cytotoxic domain, wherein said targeting domain specifically targets said polypeptide to said tissue, organ or cell and said first cytotoxic domain exerts its cytotoxic effect through a mechanism independent of the mechanism through which said second cytotoxic domain exerts its cytotoxic effect.

17. ) The method of claim 16 wherein said tissue, organ or cell is a diseased, injured or infected tissue, organ or cell.

18. ) The method of claim 17 wherein said diseased, injured or infected tissue, organ or cell is a cancerous tissue, organ or cell.

19. ) The method of claim 18 wherein said cancerous tissue, organ or cell is a tumor.