NZ774167A - Therapeutic nuclease compositions and methods - Google Patents

Therapeutic nuclease compositions and methods

Info

Publication number
NZ774167A
NZ774167A NZ774167A NZ77416712A NZ774167A NZ 774167 A NZ774167 A NZ 774167A NZ 774167 A NZ774167 A NZ 774167A NZ 77416712 A NZ77416712 A NZ 77416712A NZ 774167 A NZ774167 A NZ 774167A
Authority
NZ
New Zealand
Prior art keywords
domain
polypeptide
interferon
modified
rnase
Prior art date
Application number
NZ774167A
Inventor
Jeffrey Ledbetter
Martha Hayden-Ledbetter
Keith Elkon
Xizhang Sun
Original Assignee
Univ Washington
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Univ Washington filed Critical Univ Washington
Priority claimed from NZ753414A external-priority patent/NZ753414A/en
Publication of NZ774167A publication Critical patent/NZ774167A/en

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Disclosed is a hybrid nuclease molecule comprising a first nuclease domain and a modified Fc domain, wherein the first nuclease domain is operatively coupled to the Fc domain and wherein the Fc domain is modified such that the molecule has reduced cytotoxicity relative to a hybrid nuclease molecule having an unmodified Fc domain.

Claims (34)

We claim:
1. Use of a polypeptide comprising an RNase domain and a modified Fc domain in the manufacture of a medicament for reducing or inhibiting interferon (IFN) production in a subject, wherein the RNase domain is operatively coupled to the modified Fc domain, wherein the modified Fc domain includes a P238S mutation and a P331S mutation, and wherein the polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 96, 92, 62, or 78.
2. The use of claim 1, wherein the polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 96.
3. Use of a polypeptide comprising an RNase domain, a DNase domain, and a modified Fc domain in the manufacture of a medicament for reducing or inhibiting interferon (IFN) production in a subject, wherein the RNase domain and the DNase domain are operatively coupled to the modified Fc domain, wherein the modified Fc domain includes a P238S mutation and a P331S mutation, and wherein the polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 94 or 98.
4. The use of claim 3, wherein the polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 98.
5. The use of any one of claims 1-4, wherein the interferon is a type I interferon.
6. The use of any one of claims 1-4, wherein the interferon is interferon-α.
7. The use of any one of claims 1-6, wherein the Fc domain has decreased binding to Fcγ receptors on human cells.
8. The use of any one of claims 1-7, wherein the polypeptide has at least 1, 2, 3, 4, or 5-fold less cytotoxicity relative to a polypeptide having wild type Fc domain.
9. The use of any one of claims 1-8, wherein the polypeptide degrades: (a) circulating RNA, DNA, or RNA and DNA; and/or (b) RNA, DNA, or RNA and DNA in immune complexes.
10. The use of any one of claims 1-9, wherein the polypeptide has increased serum half-life relative to the RNase domain alone.
11. The use of any one of claims 1-9, wherein the activity of the RNase is not less than 9-fold less than the activity of a control RNase molecule.
12. The use of any one of claims 1-9, wherein the activity of the RNase is equal to the activity of a control RNase molecule.
13. The use of any one of claims 3-13, wherein the activity of the DNase is not less than 9- fold less than the activity of a control DNase molecule.
14. The use of any one of claims 3-13, wherein the activity of the DNase is equal to the activity of a control DNase molecule.
15. The use of any one of claims 3-13, wherein the polypeptide has increased serum half-life relative to the DNase domain alone.
16. The use of any one of claims 1-15, wherein the polypeptide is a dimeric polypeptide.
17. The use of claim 16, wherein the dimeric polypeptide is a homodimer.
18. The use of any one of claims 1-17, wherein the production of interferon is inhibited.
19. The use of any one of claims 1-17, wherein the production of interferon is reduced.
20. The use of any one of claims 1-19, wherein the medicament further comprises a pharmaceutically acceptable carrier.
21. The use of any one of claims 1-20, wherein the medicament is formulated for intravenous administration.
22. Use of a dimeric polypeptide comprising a first polypeptide sequence and a second polypeptide sequence in the manufacture of a medicament for reducing or inhibiting interferon (IFN) production in a subject, wherein the first polypeptide sequence comprises an RNase domain and a modified Fc domain, wherein the RNase domain is operatively coupled to the modified Fc domain, wherein the modified Fc domain includes a P238S mutation and a P331S mutation, and wherein the first polypeptide sequence comprises an amino acid sequence set forth in SEQ ID NO: 96, 92, 62, or 78.
23. The use of claim 22, wherein the dimeric polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 96.
24. Use of a dimeric polypeptide comprising a first polypeptide sequence and a second polypeptide sequence in the manufacture of a medicament for reducing or inhibiting interferon (IFN) production in a subject, wherein the first polypeptide sequence comprises an RNase domain, a DNase domain, and a modified Fc domain, wherein the RNase domain and the DNase domain are operatively coupled to the modified Fc domain, wherein the modified Fc domain includes a P238S mutation and a P331S mutation, and wherein the first polypeptide sequence comprises an amino acid sequence set forth in SEQ ID NO: 94 or 98.
25. The use of claim 24, wherein the dimeric polypeptide comprises an amino acid sequence set forth in SEQ ID NO: 98.
26. The use of any one of claims 22-25, wherein the dimeric polypeptide is a homodimer.
27. The use of any one of claims 22-26, wherein the interferon is a type I interferon.
28. The use of any one of claims 22-26, wherein the interferon is interferon-α.
29. The use of any one of claims 22-28, wherein the production of interferon is inhibited.
30. The use of any one of claims 22-28, wherein the production of interferon is reduced.
31. The use of any one of claims 22-30, wherein the medicament further comprises a pharmaceutically acceptable carrier.
32. The use of any one of claims 22-31, wherein the medicament is formulated for intravenous administration.
33. A method for producing the dimer of any one of claims 22-32, comprising: providing a host cell comprising a nucleic acid sequence that encodes the dimeric polypeptide, and maintaining the host cell under conditions in which the dimer is expressed, and wherein the host cell is not within a human.
34. The method of claim 33, further comprising obtaining the dimer. University of Washington By the Attorneys for the Applicant SPRUSON & FERGUSON
NZ774167A 2011-04-29 2012-04-27 Therapeutic nuclease compositions and methods NZ774167A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161480961P 2011-04-29 2011-04-29
US201261617241P 2012-03-29 2012-03-29
NZ753414A NZ753414A (en) 2011-04-29 2012-04-27 Therapeutic nuclease compositions and methods

Publications (1)

Publication Number Publication Date
NZ774167A true NZ774167A (en) 2022-12-23

Family

ID=84527796

Family Applications (1)

Application Number Title Priority Date Filing Date
NZ774167A NZ774167A (en) 2011-04-29 2012-04-27 Therapeutic nuclease compositions and methods

Country Status (1)

Country Link
NZ (1) NZ774167A (en)

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Free format text: PATENT RENEWED FOR 9 YEARS UNTIL 27 APR 2025 BY SPRUSON + FERGUSON PTY LTD

Effective date: 20230602