IP Library › Patent Application 14167489
Patent Application
App. No. 14/167,489

TRIBONECTINS

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Patent No.
US None
App. No.
14/167,489
Abstract

The invention features a tribonectin and a method of tribosupplementation carried out by administering tribonectins directly to an injured or arthritic joint.

Claims (47)

1 . A tribonectin comprising a polypeptide the amino acid sequence of which comprises at least one but less than 76 subunits, wherein

(a) each subunit comprises at least 7 amino acids; and

(b) the amino acid sequence of said subunit is at least 50% identical to SEQ ID NO:3, wherein a non-identical amino acid is a conservative amino acid substitution.

2 . The tribonectin of claim 1 , wherein the amino acid sequence of said subunit is SEQ ID NO:3.

3 . The tribonectin of claim 1 , wherein said tribonectiri further comprises one or more repeats of the amino acid sequence of SEQ ID NO:4.

4 . The tribonectin of claim 1 , wherein said tribonectin is characterized as reducing the coefficient of friction between bearing surfaces.

5 . The tribonectin of claim 1 , wherein said tribonectin is characterized as reducing the coefficient of friction between bearing surfaces in vitro.

6 . The tribonectin of claim 1 , wherein said tribonectin is characterized as reducing the coefficient of friction between bearing surfaces in vivo.

7 . The tribonectin of claim 1 , wherein said tribonectin does not substantially increase the viscosity of a solution to which it is added.

8 . The tribonectin of claim 1 , wherein said tribonectin comprises an O-linked oligosaccharide.

9 . The tribonectin of claim 1 , wherein said oligosaccharide is an N-acetylgalactosamine-galactose.

10 . The tribonectin of claim 1 , wherein at least 10% of said tribonectin is glycosylated.

11 . The tribonectin of claim 1 , wherein at least 40% of said tribonectin is glycosylated.

12 . The tribonectin of claim 1 , wherein the molecular weight of said tribonectin is in the range of 200-280 kDa.

13 . The tribonectin of claim 1 , wherein said polypeptide comprises a fragment of megakaryocyte stimulating factor.

14 . The triboriectin of claim 1 , wherein said polypeptide comprises an amino acid sequence that is at least 50% identical to the sequence of residues 200-1140, inclusive, of SEQ ID NO:1.

15 . The tribonectin of claim 14 , wherein said polypeptide comprises the amino acid sequence of residues 200-1140, inclusive, of SEQ ID N 0 :1.

16 . The tribonectin of claim 1 , wherein said polypeptide comprises an amino acid sequence that is at least 50% identical to the sequence of residues 200-1167, inclusive, of SEQ ID NO:1.

17 . The tribonectin of claim 16 , wherein said polypeptide comprises the amino acid sequence of residues 200-1167, inclusive, of SEQ ID NO:1.

18 . The tribonectin of claim 1 , wherein said polypeptide comprises an amino acid sequence that is at least 50% identical to the sequence of residues 200-1212, inclusive, of SEQ ID NQ:1.

19 . The tribonectin of claim 18 , wherein said polypeptide comprises the amino acid sequence of residues 200-1212, inclusive, of SEQ ID NO:1.

20 . The tribonectjn of claim 1 , wherein said polypeptide comprises an amino acid sequence that is at least 50% identical to the sequence of residues 200-1263, inclusive, of SEQ ID NO:1.

21 . The tribonectin of claim 20 , wherein said polypeptide comprises the amino acid sequence of residues 200-1263, inclusive, of SEQ ID NO:1.

22 . The tribonectin of claim 1 , wherein said polypeptide lacks the amino acid sequence of residues 1-24, inclusive, of SEQ ID NO:1.

23 . The tribonectin of claim 1 , wherein said polypeptide lacks the amino acid sequence of residues 67-104, inclusive of SEQ ID NO:1.

24 . An isolated nucleic acid molecule encoding a tribonectin.

25 . The nucleic acid of claim 24 , wherein said nucleic acid comprises the sequence of nucleotides 631-3453, inclusive, of SEQ ID NO:2.

26 . A method of lubricating a mammalian joint, comprising contacting said joint with the tribonectin of claim 1 .

27 . The method of claim 26 , wherein said joint is an articulating joint of a human.

28 . The method of claim 26 , wherein said joint is an articulating joint of a dog.

29 . The method of claim 26 , wherein said joint is an articulating joint of a horse.

30 . The method of claim 26 , wherein said tribonectin is administered intra-articularly.

31 . A method of lubricating a mammalian joint, comprising contacting said joint with the nucleic acid of claim 24 .

32 . A biocompatible composition comprising a tribonectin, wherein said composition is in a form suitable for the inhibition of tissue adhesion formation.

33 . The composition of claim 32 , wherein said tribonectin is in the form of a membrane, foam, gel, or fiber.

34 . A method inhibiting adhesion formation between a first surface and a second surface in a mammal, said method comprising placing a tribonectin between said first and second surfaces in an amount sufficient to prevent adhesion of said surfaces in said mammal.

35 . The method of claim 34 , wherein said first surface and said second surface are both injured tissues of said mammal.

36 . The method of claim 34 , wherein said first or said second surface is an artificial device.

37 . The method of claim 36 , wherein said artificial device is an orthopedic implant.

38 . The method of claim 34 , wherein said tribonectin is in the form of a membrane, foam, gel, or fiber.

39 . The method of claim 34 , wherein said injury is due to a surgical incision.

40 . The method of claim 34 , wherein said injury is due to trauma.

41 . A method for diagnosing an osteoarthritis or a predisposition thereto in a mammal, comprising measuring the amount of a fragment of megakaryocyte stimulating factor in a biological sample derived from said mammal, wherein an increase in said amount compared to a control indicates that said mammal suffers from osteoarthritis or is predisposed to developing osteoarthritis.

42 . The method of claim 41 , wherein said biological sample is synovial fluid, blood, serum, or urine.

43 . The method of claim 41 , wherein said MSF fragment comprises the amino acid sequence of SEQ ID NO:3.

44 . The method of claim 41 , wherein said MSF fragment comprises the amino acid sequence of SEQ ID NO:5.

45 . The method of claim 41 , wherein said MSF fragment comprises the amino acid sequence of SEQ ID NO:6.