Methods of enhancing functioning of the large intestine
Assignee1149336 Ontario Inc.
InventorDaniel J. Drucker
Life of this patent
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Abstract
The invention relates to glucagon-related peptides and their use for the prevention or treatment of disorders involving the large intestine. In particular, it has now been demonstrated that GLP-2 and peptidic agonists of GLP-2 can cause proliferation of the tissue of large intestine. Thus, the invention provides methods of proliferating the large intestine in a subject in need thereof. Further, the methods of the invention are useful to treat or prevent inflammatory conditions of the large intestine, including inflammatory bowel diseases.
Claims21
1-14. (canceled)
A method for treating a subject to enhance functioning of the large intestine comprising the step of delivering to the large intestine of the subject an effective amount of an intestinotrophic GLP-2 analog of SEQ ID NO:
- 1, wherein
- a) position 2 of the analog is an amino acid other than Ala,
- b) positions 1, 4, 6, 7, 9, 12-15, 17-23, 25-27, and 29-33 of the analog correspond to the amino acids of SEQ ID NO:
- 1;
- c) position 3 of the analog is optionally an amino acid other than Asp, wherein the amino acid other than Asp confers relative resistance to DPP-IV mediated cleavage;
- d) position 5 of the analog is optionally an amino acid other than Ser;
- e) position 8 of the analog is optionally an amino acid other than Asp;
- f) position 10 of the analog is optionally an amino acid other than Met;
- g) position 16 of the analog of SEQ ID NO:
- 1 optionally consists of an amino acid other than Asn;
- and
- h) position 28 of the analog is optionally an amino acid other than Gln.
A method for treating a subject having, or at risk of developing, a condition in which functioning of the large intestine is impaired to enhance functioning of the large intestine comprising the steps of:
- a) obtaining an intestinotrophic GLP-2 analog of SEQ ID NO:
- 1, wherein
- i. position 2 of the analog is an amino acid other than Ala;
- ii. positions 1, 4, 6, 7, 9, 12-15, 17-23, 25-27, and 29-33 of the analog correspond to the amino acids of SEQ ID NO:
- 1;
- iii. position 3 of the analog is optionally an amino acid other than Asp, wherein the amino acid other than Asp confers relative resistance to DPP-IV mediated cleavage;
- iv. position 5 of the analog is optionally an amino acid other than Ser;
- v. position 8 of the analog is optionally an amino acid other than Asp;
- vi. position 10 of the analog is optionally an amino acid other than Met;
- vii. position 16 of the analog is optionally an amino acid other than Asn;
- viii. position 24 of the analog is optionally an amino acid other than Asn;
- ix. position 28 of the analog is optionally an amino acid other than Gln;
- and
- b) delivering the analog to the large intestine of the subject in an amount effective to ameliorate the condition.
A kit for use in treating a subject having, or at risk of developing, a condition in which functioning of the large intestine is impaired to enhance functioning of the large intestine comprising:
- a) a lyophilized formulation of a GLP-2 analog of SEQ ID NO:
- 1 comprising intestinotrophic activity, wherein
- i. position 2 of the analog is an amino acid other than Ala;
- ii. positions 1, 4, 6, 7, 9, 12-15, 17-23, 25-27, and 29-33 of the analog correspond to amino acids of SEQ ID NO:
- 1;
- iii. position 3 of the analog of SEQ ID NO:
- 1 is optionally an amino acid other than Asp, wherein the amino acid other than Asp confers relative resistance to DPP-IV mediated cleavage,
- iv. position 5 of the analog is optionally an amino acid other than Ser;
- v. position 8 of the analog is optionally an amino acid other than Asp;
- vi. position 10 of the analog is optionally an amino acid other than Met;
- vii. position 16 of the analog is optionally an amino acid other than Asn;
- viii. position 24 of the analog is optionally an amino acid other than Asn;
- ix. position 28 of the analog is optionally an amino acid other than Gln;
- b) a vial of sterile water for reconstitution;
- and
- c) instructions directing reconstitution.
Dependencies are inferred from the claim text.