Modified Tamm-Horsfall protein and related compositions and methods of use

Patent metadata

Field	Value
Publication number	US-11053290-B2
Application number	US-201615771036-A
Country	US
Kind code	B2
Filing date	Oct 28, 2016
Priority date	Oct 30, 2015
Publication date	Jul 6, 2021
Grant date	Jul 6, 2021

Abstract

Embodiments of the present disclosure provide polypeptides, related materials and compositions, and methods for their use. In certain embodiments, the present disclosure provides a monomeric Tamm-Horsfall Protein polypeptide, or a biologically active truncation thereof. Other embodiments provide polynucleotides encoding a polypeptide described herein, nucleic acid expression vectors including the polynucleotides, and recombinant host cells including the expression vector. Yet other embodiments provide pharmaceutical compositions including a polypeptide described herein. Also provided are methods for treating a renal disease, disorder, or condition in a subject and/or modulating an immune response in a subject.

First claim

What is claimed is:

1. A purified or isolated polypeptide consisting of an amino acid sequence at least 95% identical to an amino acid sequence chosen from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO:6, and SEQ ID NO: 7.

2. The purified or isolated polypeptide of claim 1 , wherein the purified or isolated polypeptide consists of an amino acid sequence chosen from SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO:6, and SEQ ID NO: 7.

3. A pharmaceutical composition comprising the purified or isolated polypeptide of claim 1 and a pharmaceutically acceptable carrier.

4. The pharmaceutical composition of claim 3 , further comprising a purified or isolated polypeptide comprising an amino acid sequence at least 85% identical to an amino acid sequence according to SEQ ID NO: 1.

5. A method for treating at least one renal disease, disorder, or condition in a subject, the method comprising administering to the subject an effective amount of the purified or isolated polypeptide of claim 1 , or both the purified or isolated polypeptide of claim 1 and a purified or isolated polypeptide comprising an amino acid sequence at least 85% identical to an amino acid sequence according to SEQ ID NO: 1, wherein the at least one renal disease, disorder, of condition comprises at least one of: acute kidney injury, sepsis, transplant rejection, and chronic kidney disease.

6. The method according to claim 5 , wherein the polypeptide or the pharmaceutical composition is administered orally, intravenously, intraperitoneally, intramuscularly, or subcutaneously.

7. The method according to claim 5 , wherein the effective amount is between about 0.2 mg/kg and about 10.0 mg/kg of the polypeptide.

8. The method according to claim 5 , wherein the effective amount is between about 0.2 mg/kg and about 3.0 mg/kg of the polypeptide.

9. A method for treating at least one renal disease, disorder, or condition in a subject, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 3 , or a pharmaceutical composition of claim 3 further comprising a polypeptide comprising an amino acid sequence at least 85% identical to an amino acid sequence according to SEQ ID NO: 1, wherein the at least one renal disease, disorder, of condition comprises at least one of: acute kidney injury, sepsis, transplant rejection, and chronic kidney disease.

10. The method according to claim 9 , wherein the polypeptide or the pharmaceutical composition is administered orally, intravenously, intraperitoneally, intramuscularly, or subcutaneously.

11. The method according to claim 9 , wherein the effective amount is between about 0.2 mg/kg and about 10.0 mg/kg of the polypeptide.

12. The method according to claim 9 , wherein the effective amount is between about 0.2 mg/kg and about 3.0 mg/kg of the polypeptide.

13. An immunogenic composition comprising at least one immunogenic agent and the purified or isolated polypeptide of claim 1 .

14. A method for enhancing an immune response to an immunogenic composition in a subject, the method comprising administering to the subject an effective amount of the purified or isolated polypeptide of claim 1 .

15. A purified or isolated polypeptide consisting of an amino acid sequence at least 95% identical to SEQ ID NO: 7.

16. A pharmaceutical composition comprising the purified or isolated polypeptide of claim 15 and a pharmaceutically acceptable carrier.

17. A method for treating at least one renal disease, disorder, or condition in a subject, the method comprising administering to the subject an effective amount of the purified or isolated polypeptide of claim 15 .

18. The purified or isolated polypeptide of claim 1 , further comprising a polypeptide half-life increasing compound or a peptide purification tag linked to the isolated polypeptide.

19. The purified or isolated polypeptide of claim 15 , further comprising polypeptide half-life increasing compound or a peptide purification tag linked to the isolated polypeptide.

Assignees

• Univ Indiana Res & Tech Corp
• The Us Gov As Represented By The Department Of Veterans Affair

Inventors

• Ashkar Tarek Maurice
• Micanovic Radmila

Classifications

• C07K14/435 Primary

  from animals; from humans · CPC title

• A61K35/00

  Medicinal preparations containing materials or reaction products thereof with undetermined constitution · CPC title

• A61K38/00

  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 title

• A61P13/12

  of the kidneys · CPC title

• C07K14/47 Primary

  from mammals · CPC title