US2017190748A1PendingUtilityA1
Anti-inflammatory proteins and peptides and methods of preparation and use thereof
Assignee: MANUKAMED HOLDINGS LTD PARTNERSHIPPriority: Jun 22, 2012Filed: Jan 11, 2017Published: Jul 6, 2017
Est. expiryJun 22, 2032(~5.9 yrs left)· nominal 20-yr term from priority
A61P 9/00A61P 3/10A61P 39/06A61P 37/02A61P 37/08A61P 37/06A61P 31/00A61P 31/12A61P 29/00A61P 27/02A61P 25/28A61P 31/22A61P 35/00A61P 11/06A61P 17/02A61P 15/00A61P 11/00A61P 19/02A61P 1/04A61P 17/06A61P 25/00A61P 17/00A61K 38/00C12Q 1/37G01N 2333/43565C07K 14/8139C07K 5/1019C07K 5/0808A61K 38/1767A61K 35/644C07K 5/1013A61L 2300/41G01N 2333/96466A61L 2300/252C07K 5/0812A61L 15/32G01N 2500/04G01N 2500/20C07K 14/43572C07K 5/1024C07K 5/0815A61L 15/44A61L 2300/25C12Y 304/22001
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Claims
Abstract
The present disclose relates to anti-inflammatory proteins/peptides, their uses, methods of preparation and methods of their detection. In particular, the invention relates to major royal jelly proteins modified by methyglyoxal and fragments thereof from a Leptospermum derived honey and royal jelly.
Claims
exact text as granted — not AI-modified1 .- 24 . (canceled)
25 . An isolated functional fragment of a major royal jelly protein (MRJP), which has anti-inflammatory capacity, and which is not a naturally occurring functional fragment of a major royal jelly protein, wherein a lysine or arginine amino acid residue of the functional fragment has been chemically modified by methylglyoxal (MGO), and wherein:
a. the functional fragment comprises an amino acid sequence selected from the group consisting of:
i.
(SEQ ID NO: 11)
KNNNQNDN;
ii.
(SEQ ID NO: 12)
KLH;
iii.
(SEQ ID NO: 13)
KSNNRHNNND;
iv.
(SEQ ID NO: 14)
KHNN;
v.
(SEQ ID NO: 15)
KNQAHLD;
vi.
(SEQ ID NO: 16)
KNTRCISP;
vii.
(SEQ ID NO: 17)
KTNFFSIFL;
viii.
(SEQ ID NO: 64)
PFKISIHL ;
ix.
(SEQ ID NO: 69)
NQKNNNQNDN ;
(SEQ ID NO: 66)
NQKN ;
x.
(SEQ ID NO: 71)
SKLH ;
xi.
(SEQ ID NO: 81)
QNKHNN ;
(SEQ ID NO: 80)
KH ;
xii.
(SEQ ID NO: 84)
LVK ;
xiii.
(SEQ ID NO: 86)
LIR ;
xiv.
(SEQ ID NO: 127)
FDR ;
xv.
(SEQ ID NO: 128)
HNIR ;
and
xvi.
(SEQ ID NO: 130)
FTK
(SEQ ID NO: 137)
QNGNK ;
or
b. the functional fragment comprises a peptide analogue selected from the group consisting of:
i.
(SEQ ID NO: 24)
Ac-NQKNNNQNDN-OH ;
ii.
(SEQ ID NO: 27)
Ac-NQKN-OH ;
iii.
(SEQ ID NO: 31)
Ac-SKLH-OH ;
iv.
(SEQ ID NO: 43)
Ac-QNKHNN-OH ;
(SEQ ID NO: 45)
Ac-KH-OH ;
v.
(SEQ ID NO: 48)
Ac-LVK-OH ;
vi.
(SEQ ID NO: 51)
A c-LIR-OH ;
vii.
(SEQ ID NO: 53)
Ac-FDR-OH ;
viii.
(SEQ ID NO: 59)
Ac-HNIR-OH ;
ix.
(SEQ ID NO: 88)
H-FTK-OH ;
and
x.
(SEQ ID NO: 106)
Ac-QNGNK-OH .
26 .- 29 . (canceled)
30 . The isolated functional fragment of claim 25 , which is chemically synthesized.
31 . The isolated functional fragment of claim 25 , which is recombinantly produced.
32 . A composition comprising the isolated functional fragment of claim 25 , or an analogue thereof.
33 . A wound dressing comprising a functional fragment of a major royal jelly protein (MRJP); wherein the functional fragment has anti-inflammatory activity; wherein the functional fragment has been isolated, enriched, chemically synthesized, or recombinantly produced; wherein a lysine or arginine amino acid residue of the functional fragment has been chemically modified by methylglyoxal (MGO); and wherein:
a. the functional fragment comprises an amino acid sequence selected from the group consisting of:
i.
(SEQ ID NO: 11)
KNNNQNDN;
ii.
(SEQ ID NO: 12)
KLH;
iii.
(SEQ ID NO: 13)
KSNNRHNNND;
iv.
(SEQ ID NO: 14)
KHNN;
(SEQ ID NO: 15)
KNQAHLD;
vi.
(SEQ ID NO: 16)
KNTRCISP;
vii.
(SEQ ID NO: 17)
KTNFFSIFL;
viii.
(SEQ ID NO: 64)
PFKISIHL ;
ix.
(SEQ ID NO: 69)
NQKNNNQNDN ;
(SEQ ID NO: 66)
NQKN ;
x.
(SEQ ID NO: 71)
SKLH ;
xi.
(SEQ ID NO: 81)
QNKHNN ;
(SEQ ID NO: 80)
KH ;
xii.
(SEQ ID NO: 84)
LVK ;
xiii.
(SEQ ID NO: 86)
LIR ;
xiv.
(SEQ ID NO: 127)
FDR ;
xv.
(SEQ ID NO: 128)
HNIR ;
and
xvi.
(SEQ ID NO: 130)
FTK
(SEQ ID NO: 137)
QNGNK ;
or
b. the functional fragment comprises a peptide analogue selected from the group consisting of:
i.
(SEQ ID NO: 24)
Ac-NQKNNNQNDN-OH ;
ii.
(SEQ ID NO: 27)
Ac-NQKN-OH ;
iii.
(SEQ ID NO: 31)
Ac-SKLH-OH ;
iv.
(SEQ ID NO: 43)
Ac-QNKHNN-OH ;
(SEQ ID NO: 45)
Ac-KH-OH ;
v.
(SEQ ID NO: 48)
Ac-LVK-OH ;
vi.
(SEQ ID NO: 51)
Ac-LIR-OH ;
vii.
(SEQ ID NO: 53)
Ac-FDR-OH ;
viii.
(SEQ ID NO: 59)
Ac-HNIR-OH ;
ix.
(SEQ ID NO: 88)
H-FTK-OH ;
and
x.
(SEQ ID NO: 106)
Ac-QNGNK-OH .
34 .- 44 . (canceled)
45 . A method of inhibiting Cathepsin B activity in a cellular tissue, comprising the step of contacting the cellular tissue with a functional fragment of a major royal jelly protein (MRJP); wherein the functional fragment has been isolated, enriched, synthesized, or recombinantly produced; wherein a lysine or arginine amino acid residue of the functional fragment has been chemically modified by methylglyoxal (MGO); and wherein
a. the functional fragment comprises an amino acid sequence selected from the group consisting of:
i.
(SEQ ID NO: 10)
KISIHL ;
ii.
(SEQ ID NO: 11)
KNNNQNDN ;
iii.
(SEQ ID NO: 12)
KLH ;
iv.
(SEQ ID NO: 13)
KSNNRHNNND ;
v.
(SEQ ID NO: 14)
KHNN ;
vi.
(SEQ ID NO: 15)
KNQAHLD ;
vii.
(SEQ ID NO: 16)
KNTRCISP ;
viii.
(SEQ ID NO: 17)
KTNFFSIFL ;
ix.
(SEQ ID NO: 64)
PFKISIHL ;
x.
(SEQ ID NO: 69)
NQKNNNQNDN ;
(SEQ ID NO: 66)
NQKN ;
xi.
(SEQ ID NO: 71)
SKLH ;
xii.
(SEQ ID NO: 81)
QNKHNN ;
(SEQ ID NO: 80)
KH ;
xiii.
(SEQ ID NO: 84)
LVK ;
xiv.
(SEQ ID NO: 86)
LIR ;
xv.
(SEQ ID NO: 127)
FDR ;
xvi.
(SEQ ID NO: 128)
HNIR ;
and
xvii.
(SEQ ID NO: 130)
FTK
(SEQ ID NO: 137)
QNGNK ;
or
b. the functional fragment comprises a peptide analogue selected from the group consisting of:
i.
(SEQ ID NO: 24)
Ac-NQKNNNQNDN-OH ;
ii.
(SEQ ID NO: 27)
Ac-NQKN-OH ;
iii.
(SEQ ID NO: 31)
Ac-SKLH-OH ;
iv.
(SEQ ID NO: 43)
Ac-QNKHNN-OH ;
(SEQ ID NO: 45)
Ac-KH-OH ;
v.
(SEQ ID NO: 48)
Ac-LVK-OH ;
vi.
(SEQ ID NO: 51)
Ac-LIR-OH ;
vii.
(SEQ ID NO: 53)
Ac-FDR-OH ;
viii.
(SEQ ID NO: 59)
Ac-HNIR-OH ;
ix.
(SEQ ID NO: 88)
H-FTK-OH ;
and
x.
(SEQ ID NO: 106)
Ac-QNGNK-OH .
46 .- 53 . (canceled)
54 . The method of claim 45 , wherein the method reduces inflammation in the cellular tissue.
55 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: an inflammatory disorder, a cardiovascular disorder, a neurological disorder, a pulmonary disorder, a proliferative disorder, an infectious disease or associated syndrome, an allergic, immunological or autoimmune disorder, and inflammation associated with a wound.
56 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: rheumatoid arthritis and polyarthritis.
57 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: Alzheimer's disease, progressive multifocal leukoencephalopathy (PML), and multiple sclerosis.
58 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: asthma, bronchitis, bronchopneumonia, adult respiratory distress syndrome, emphysema, and chronic obstructive pulmonary disease (COPD).
59 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: genital herpes, Epstein-Barr virus (EBV) infection, EBV associated encephalitis, and cytomegalovirus (CMV) associated choreoretinitis.
60 . The method of claim 54 , wherein the inflammation is associated with one or more of the group consisting of: Wegeneres granulomatosis, choreoretinitis, encephalitis, gastroenteritis, uveitis, psoriasis, and dermatitis.
61 . The method of claim 54 , wherein the inflammation is associated with melanoma.
62 . The method of claim 55 , wherein the wound is one or more of the group consisting of: a diabetic ulcer, fungating wound, puncture wound, cut, bite, and surgical wound.
63 . The method of claim 54 , wherein the method comprises administration of the functional fragment to a subject, and wherein the administration includes one or more of oral, topical, and parenteral administration.
64 . The method of claim 54 , wherein the method comprises administration of the functional fragment to a subject, and wherein the administration includes one or more of intravenous, intravitreal, or intramuscular administration.
65 . The method of claim 54 , wherein the method reduces the rate of phagocytosis by immune system cells.
66 . The method of claim 54 , wherein the method inhibits receptors for phagocytosis on immune system cells.
67 . The method of claim 54 , wherein the method reduces respiratory burst and release of reactive oxygen species from inflammatory cells.Join the waitlist — get patent alerts
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