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CN-122003244-A - Composition comprising ATP degrading enzyme and use thereof

CN122003244ACN 122003244 ACN122003244 ACN 122003244ACN-122003244-A

Abstract

Provided herein, inter alia, are compositions and methods for treating and/or preventing conditions associated with skin and/or oral inflammation via the use of exogenously administered ATP degrading enzymes, such as the NTPD enzyme of the gda1—cd39 superfamily, or phosphatases that are capable of functioning in physiologically relevant pH ranges.

Inventors

  • L.M. Beby
  • R. KUMAR
  • A.D.Liu
  • A.A. Pryor
  • D. Vavelin
  • WEI WEI

Assignees

  • 丹尼斯科美国公司
  • 美国丹尼斯科公司

Dates

Publication Date
20260508
Application Date
20240919
Priority Date
20230920

Claims (20)

  1. 1. A composition comprising an ATP degrading enzyme and at least one oral care component and/or at least one skin care component.
  2. 2. The composition of claim 1, wherein the enzyme is active at least at about pH 3.5 to pH 9.
  3. 3. The composition of claim 1 or claim 2, wherein the enzyme comprises apyrase.
  4. 4. The composition of claim 1 or claim 2, wherein the enzyme comprises an acid phosphatase.
  5. 5. The composition of any one of claims 1-3, wherein the enzyme comprises a gda1_cd39 superfamily member and is not potato triphosphates apyrase.
  6. 6. The composition of any one of claims 1-5, wherein the enzyme is not a mammalian NTPD enzyme.
  7. 7. The composition of any one of claims 1-6, wherein the enzyme is capable of reducing the level of one or more inflammatory mediators by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% as compared to a reference.
  8. 8. The composition of claim 7, wherein the one or more inflammatory mediators comprise TNF- α, IL-6, IL17A, IFN γ, IL-8, or a combination thereof.
  9. 9. The composition of any one of claims 1-8, wherein the enzyme is capable of reducing the level of cell death by at least 1%, at least 5%, at least 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% as compared to a reference.
  10. 10. The composition of any one of claims 1-9, wherein the enzyme comprises a polypeptide that is at least 40%、41%、42%、43%、44%、45%、46%、47%、48%、49%、50%、51%、52%、53%、54%、55%、56%、57%、58%、59%、60%、61%、62%、63%、64%、65%、66%、67%、68%、69%、70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99% or 100% identical to the amino acid sequence of any one of SEQ ID NO: 19、SEQ ID NO: 34（CRC22110）、SEQ ID NO: 51、SEQ ID NO: 52、SEQ ID NO: 53、SEQ ID NO: 57、SEQ ID NO: 58、SEQ ID NO: 59、SEQ ID NO: 30、SEQ ID NO: 45 and SEQ ID No. 93.
  11. 11. The composition of any one of claims 1-10, wherein the enzyme comprises a polypeptide having one or more modifications.
  12. 12. The composition of any one of claims 1-11, wherein the enzyme comprises a polypeptide having one or more modifications within the amino acid sequence of SEQ ID No. 19 or SEQ ID No. 34 (CRC 22110).
  13. 13. The composition of any one of claims 1-11, wherein the enzyme comprises a polypeptide comprising a truncation at the C-terminus of SEQ ID No. 19 or SEQ ID No. 34 (CRC 22110).
  14. 14. The composition of any one of claims 1-11, wherein the enzyme comprises a polypeptide having one or more modifications within the amino acid sequence of SEQ ID No. 93 or SEQ ID No. 45.
  15. 15. The composition of any one of claims 1-14, wherein the oral care component comprises a toothpaste, a prophylactic paste, a dentifrice, a tooth polish, a tooth gel, a chewing gum, a lozenge, a mouthwash, an oral rinse, a whitening strip, a patch, a suspension, an emulsion, a hydrogel, a paste, a multi-phase solution, a lacquered gel, a varnish, a veneer, and a tube, syringe, or dental tray comprising a gel or paste, or a gel or paste coated on an application support such as a dental floss or toothbrush.
  16. 16. The composition of any one of claims 1-15, wherein the skin care component comprises an ointment, essence, hydrogel, solution, dressing, moisturizer, exfoliant, body wash, eye cream, sun, skin cream, cleanser, skin lotion, artificial skin, probiotic skin care component, or spray.
  17. 17. The composition of any one of claims 1-16, wherein the skin and/or oral care component comprises a wound care component.
  18. 18. A nucleic acid encoding the enzyme of any one of claims 1-17.
  19. 19. A vector comprising the nucleic acid of claim 18.
  20. 20. A recombinant host cell comprising the enzyme of any one of claims 1-17, the nucleic acid of claim 18, and/or the vector of claim 19.

Description

Composition comprising ATP degrading enzyme and use thereof The present application claims priority to chinese international patent application number PCT/CN2023/119945 filed on 9/20 of 2023, the disclosure of which is incorporated herein by reference in its entirety. Sequence listing incorporated by reference Sequence listings submitted in XML file format according to 37 c.f.r. ≡2412 are incorporated herein by reference. The xml file name is "NB42172_wo_pct_seq_list.xml", the creation date of the xml file is 2024, 9 months 12 days, and the size (in bytes) of the xml file is 149,120. Technical Field Provided herein, inter alia, are compositions and methods for treating and/or preventing conditions associated with skin and/or oral inflammation via the use of exogenously administered ATP degrading enzymes (NTPD enzymes, nucleotidases such as apyrase and gda1_cd39 superfamily members, and phosphatases). Background Skin and oral mucosa provide a first line of defense against external stimuli through their physical and immune barrier functions, where commensal microorganisms play a key role in maintenance, homeostasis and immunity. Barrier disorders caused by physical or chemical injury, environmental exposure, toxins and pathogenic microorganisms can lead to altered microenvironments, activation of immune cells, and release of pro-inflammatory molecules and mediators, including extracellular Nucleotide Triphosphates (NTPs) (e.g., extracellular ATP (eATP)) and cytokines (e.g., TNF- α, IL-1β, IL-6). Regardless of the source of the damage, the inflammatory process may lead to further barrier changes, varying degrees of tissue damage and loss of function. Treatment and/or prophylaxis against skin and oral health has historically been driven by the etiology of disorders, with possible negative effects on maintaining a steady state balance with the microbiome. Thus, there is a need for improved methods and compositions that function in a broad range of pathologies by targeting a common downstream inflammatory process, which can lead not only to increased product design efficiency, but also to the persistence and health of symbiotic microbiota. The subject matter disclosed herein addresses these needs and provides additional benefits. Disclosure of Invention Provided herein is a composition comprising an ATP degrading enzyme and at least one oral care component and/or at least one skin care component. In some embodiments, the enzyme is active at least at about pH 3.5 to pH 9. In some embodiments, the enzyme is apyrase. In some embodiments, the enzyme is a gda1—cd39 superfamily member and is not potato apyrase. In some embodiments, the enzyme is not a mammalian NTPD enzyme. In some embodiments, the enzyme is a phosphatase. In other embodiments, the enzyme is capable of reducing the level of one or more inflammatory mediators by 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% as compared to a reference. In some embodiments, the one or more inflammatory mediators are TNF- α, IL-6, IL17A, IFN gamma, IL-8, or a combination thereof. In some embodiments, the enzyme is capable of reducing the level of cell death by 10%, at least 20%, at least 30%, at least 40%, at least 50%, at least 60%, at least 70%, at least 80%, or at least 90% as compared to a reference. In some embodiments, the enzyme is a polypeptide that is at least 35%、36%、37%、38%、39%、40%、41%、42%、43%、44%、45%、46%、47%、48%、49%、50%、51%、52%、53%、54%、55%、56%、57%、58%、59%、60%、61%、62%、63%、64%、65%、66%、67%、68%、69%、70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99% or 100% identical to the amino acid sequence of either of SEQ ID NO: 19、SEQ ID NO: 34（CRC22110）、SEQ ID NO: 51、SEQ ID NO: 52、SEQ ID NO: 53、SEQ ID NO: 57、SEQ ID NO: 58、SEQ ID NO: 59、SEQ ID NO: 30、SEQ ID NO: 45 and SEQ ID NO. 93. In some of any of the embodiments, the enzyme is a polypeptide having one or more modifications. In some embodiments, the modification is a truncation. In some embodiments, the enzyme is a polypeptide having one or more modifications within the amino acid sequence of SEQ ID NO. 19 or SEQ ID NO. 34 (CRC 22110). In some embodiments, the enzyme comprises a truncated polypeptide at the C-terminus of SEQ ID NO. 19 or SEQ ID NO. 34 (CRC 22110). In some embodiments, the enzyme is a polypeptide that is at least 35%、36%、37%、38%、39%、40%、41%、42%、43%、44%、45%、46%、47%、48%、49%、50%、51%、52%、53%、54%、55%、56%、57%、58%、59%、60%、61%、62%、63%、64%、65%、66%、67%、68%、69%、70%、71%、72%、73%、74%、75%、76%、77%、78%、79%、80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99% or 100% identical to the amino acid sequence of SEQ ID NO. 51. In some embodiments, the enzyme is a polypeptide having one or more modifications within the amino acid sequence of SEQ ID NO. 93 or SEQ ID NO. 45. In some of any of the embodiments, the composition contains an oral care component that is a to