POLYPEPTIDES AND METHODS OF USE

• US 20100292161A1
• Filed: 06/16/2008
• Published: 11/18/2010
• Est. Priority Date: 06/14/2007
• Status: Active Grant

• Current Assignee: The Research Foundation for The State University of New York (State University of New York)
• Original Assignee: The Research Foundation for The State University of New York (State University of New York)
• Inventors: Clark, Richard A.
• Granted Patent: US 8,759,300 B2
• Time in Patent Office: Days
• US Class Current: 514/19.3
• 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 8/64 Proteins; Peptides; Derivatives or degradation products thereof
• CPC Class Codes: A61L 27/227 Other specific proteins or polypeptides not covered by A61L27/222, A61L27/225 or A61L27/24
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C07K 14/78 Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
• CPC Class Codes: G01N 2333/71 for growth factors; for growth regulators
• CPC Class Codes: G01N 2500/02 Screening involving studying the effect of compounds C on the interaction between interacting molecules A and B (e.g. A = enzyme and B = substrate for A, or A = receptor and B = ligand for the receptor)
• CPC Class Codes: G01N 33/5032 on intercellular interactions

Abstract

Described herein are fragments of fibronectin and vitronectin and variants thereof that have certain activities, including growth factor-binding activity. Also described are fragments of growth factors that bind to fibronectin and inhibit binding of full-length growth factors to fibronectin. Compositions containing such fragments are useful in cosmetic treatments (e.g., the treatment of wrinkles or UV photodamage of skin), and the treatment of wounds and cancer.

Claims

1-10. -10. (canceled)

11. An isolated polypeptide comprising an amino acid sequence conforming to the formula

24. The isolated polypeptide of claim 11, wherein the polypeptide comprises the sequence SHISKYIL (SEQ ID NO:

57);

SLAKKQRF (SEQ ID NO;

58);

RWRPK (SEQ ID NO;

59);

RHRNR (SEQ ID NO;

60);

PSHISKYL (SEQ ID NO;

61);

PSLAKKQRF (SEQ ID NO;

62);

PSHISKYILRWRPK (Peptide 12;

SEQ ID NO;

63);

PSLAKKQRFRHRNR (SEQ ID NO;

64);

QPSHISKYILRWRPK (Peptide 5;

SEQ ID NO;

65);

QPSHISKYILRWRPKNSVGRWKEAT (peptide 1;

SEQ ID NO;

66);

QLIS.IQQYGHQEVTRFDFTTTSTST (peptide 2;

SEQ ID NO;

67);

NGQTPIQRTIKPDVRSYTITGLQPGT (peptide 3;

SEQ ID NO;

68);

or QPSVGQQMIFEEHGFRRTTPPTTAT (peptide 4;

SEQ ID NO;

69).

32. The isolated polypeptide of claim 11, wherein the polypeptide further comprises a protecting group.

33. The isolated polypeptide of claim 32, wherein the protecting group is an acyl group, an amide, a benzyl group, a benzoyl group, or a polyethylene glycol group.

38. A nucleic acid molecule encoding the isolated polypeptide of claim 11.

39. An expression vector comprising the nucleic acid molecule of claim 38.

40. A cell comprising the expression vector of claim 39.

41. A physiologically acceptable composition comprising the isolated polypeptide of claim 11.

42. The physiologically acceptable composition of claim 41, wherein the composition is formulated for topical administration.

46. A tissue engineering construct comprising the isolated polypeptide of claim 11.

47. The tissue engineering construct of claim 46, wherein the construct comprises a natural or artificial extracellular matrix (ECM).

48. The tissue engineering construct of claim 46, wherein the construct comprises a biocompatible polymer.

55. The tissue engineering construct of claim 46, further comprising a growth factor.

58. A method of treating a patient who has cancer, the method comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 41.

59. The method of claim 58, wherein the cancer is associated with overexpression of a growth factor.

60. The method of claim 59, wherein the growth factor is a TGFβ

, a PDGF, an FGF, a KGF, a VEGF, an IGF or an NGF.

62. A method of treating a patient who has a wound, the method comprising administering to the patient a therapeutically effective amount of the physiologically acceptable composition of claim 41.

63. The method of claim 62, wherein the composition is administered as a tissue engineering construct or in association with a solid support.

64. The method of claim 63, wherein the wound is a surgical incision or extirpation, a traumatic injury, a burn, a lesion, or an ulceration of the patient'"'"'s skin, mucosa, connective tissue, fascia, ligament, tendon, cartilage, nerve or muscle or a wound to the patient'"'"'s bone.

71. A method for culturing a cell, the method comprising placing the cell in a tissue culture vessel comprising the isolated polypeptide of claim 11, wherein the cell is maintained under conditions conducive to cell survival.

12-23. -23. (canceled)

25-31. -31. (canceled)

34-37. -37. (canceled)

43-45. -45. (canceled)

49-54. -54. (canceled)

56-57. -57. (canceled)

61. (canceled)

65-70. -70. (canceled)

72-81. -81. (canceled)