US2016095935A1PendingUtilityA1
Conjugates comprising mannan and myelin basic protein (mbp)
Est. expiryJan 25, 2028(~1.5 yrs left)· nominal 20-yr term from priority
Inventors:John MatsoukasTheodoros TseliosVasso ApostolopoulosVivian TsevelekiMaria KatsaraLesley Probert
A01K 2267/0325A61K 2039/6087A61K 47/64C07K 7/08C07K 14/4713C07K 7/64A61K 2039/627A61K 39/0008A01K 2207/10A01K 2227/105A61P 37/06A61K 47/48246
38
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Claims
Abstract
A first aspect of the invention relates to a conjugate including mannan and at least one epitope comprising a peptide fragment of a protein selected from myelin basic protein (MBP), myelin oligodentrocyte glycoprotein (MOG) and proteolipid protein (PLP), said peptide fragment being in linear or cyclic form; and wherein said epitope is linked to mannan via a [(Lys-Gly) n ] bridge, where n is an integer from 1 to 10. Further aspects of the invention relate to pharmaceutical compositions comprising said conjugates, and their use in the preparation of a medicament for treating an immune disorder.
Claims
exact text as granted — not AI-modified1 . A conjugate comprising:
(i) mannan; and (ii) at least one epitope comprising a peptide fragment of myelin basic protein (MBP), said peptide fragment being in linear or cyclic form; wherein said epitope is linked to mannan via a [(Lys-Gly) n ] bridge, where n is an integer from 1 to 10.
2 . (canceled)
3 . A conjugate according to claim 1 , wherein the epitope comprises a peptide selected from MBP 83-99 , MBP 82-101 , [Ala 86 ]MBP 83-89 , [Ala 88 ]MBP 83-89 [Tyr 89 ]MBP 83-89 and MBP 110-118 , and variants thereof, in linear or cyclic form.
4 . A conjugate according to claim 1 , wherein the epitope comprises the peptide MBP 83-99 , in linear or cyclic form.
5 . A conjugate according to claim 1 , wherein the epitope corresponds to the peptide of SEQ ID NO. 1, or a variant thereof:
[SEQ ID NO. 1]
H-Glu-Asn-Pro-Val-Val-His-Phe-Phe-Lys-Asn-Ile-Val-
Thr-Pro-Arg-Thr-Pro-OH
in linear or cyclic form.
6 .- 14 . (canceled)
15 . A conjugate according to claim 1 , wherein the mannan is reduced mannan.
16 . A conjugate according to claim 1 , wherein the mannan is oxidised mannan.
17 . A conjugate according to claim 1 , wherein two or more epitopes, or cyclic counterparts thereof, are linked to mannan.
18 . A conjugate according to claim 17 wherein the epitopes (or cyclic counterparts thereof) are different.
19 . A mixture comprising two or more conjugates according to claim 1 .
20 . A mixture according to claim 19 wherein the conjugates are different.
21 . A pharmaceutical preparation comprising a conjugate according to claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.
22 .- 26 . (canceled)
27 . A method of treating an immune disorder, said method comprising administering to a subject a conjugate according to claim 1 .
28 . A method according to claim 27 wherein the immune disorder is an autoimmune disease.
29 . A method according to claim 27 wherein the immune disorder is multiple sclerosis (MS).
30 . A method according to claim 27 wherein the immune disorder is experimental autoimmune encephalomyelitis (EAE).
31 . A method of immunizing a subject against an immune disorder, said method comprising administering to a subject a conjugate according to claim 1 .
32 . A method according to claim 27 wherein the conjugate is administered in an amount sufficient to cause suppression of chronic experimental autoimmune encephalomyelitis (EAE).
33 . (canceled)
34 . A process for preparing a conjugate according to claim 1 , said process comprising the steps of:
(i) reacting an epitope comprising a peptide fragment of myelin basic protein (MBP), said peptide fragment being in linear or cyclic form, with a peptide bridge [(Lys-Gly) n ], wherein n is an integer from 1 to 10; (ii) reacting the product formed in step (i) with oxidized mannan; and (iii) optionally reducing the product formed in step (ii) to form a reduced mannan conjugate.
35 . A vaccine comprising a conjugate according to claim 1 .
36 . (canceled)
37 . A conjugate according to claim 1 further comprising:
an epitope comprising a peptide fragment of myelin oligodentrocyte glycoprotein (MOG); and
an epitope comprising a peptide fragment of proteolipid protein (PLP);
each peptide fragment being in linear or cyclic form;
wherein each epitope is linked to mannan via a [(Lys-Gly) n ] bridge, where n is an integer from 1 to 10.
38 . A conjugate according to claim 1 further comprising one of
(i) epitope comprising a peptide fragment of myelin oligodentrocyte glycoprotein (MOG); and
(ii) an epitope comprising a peptide fragment of proteolipid protein (PLP).
39 . A conjugate according to claim 5 wherein the epitope is linked to mannan via a [(Lys-Gly) 5 ] bridge.
40 . A conjugate according to claim 1 wherein the peptide has the amino acid sequence of formula (I),
ENPVVHFFK 91 NIVTP 96 RTP
(I)
wherein at least one of K 91 and P 96 is substituted by a natural or unnatural amino acid, wherein said peptide is in linear or cyclic form.
41 . A conjugate according to claim 40 wherein K 91 is substituted by an amino acid selected from A, R, E, F and Y.
42 . A conjugate according to claim 40 wherein P 96 is substituted by the amino acid A.
43 . A conjugate according to claim 40 wherein the peptide is selected from:
[R 91 , A 96 ]MBP 83-99
ENPVVHFFRNIVTARTP;
[A 91 , A 96 ]MBP 83-99
ENPVVHFFANIVTARTP;
[E 91 ]MBP 83-99
ENPVVHFFENIVTPRTP;
[F 91 ]MBP 83-99
ENPVVHFFFNIVTPRTP;
and
[Y 91 ]MBP 83-99
ENPVVHFFYNIVTPRTP.
44 . A conjugate according to claim 1 wherein the peptide is selected from the following:
peptide analogues
sequence
cyclo(83-99)MBP 83-99
SEQ ID NO. 1
cyclo(83-99)E N P V V H F F K N I V T P R T P
cyclo(83-99)[A 91 ]MBP 83-99
SEQ ID NO. 18
cyclo(83-99)E N P V V H F F A N I V T P R T P
cyclo(83-99)[R 91 ]MBP 83-99
SEQ ID NO. 19
cyclo(83-99)E N P V V H F F R N I V T P R T P
cyclo(83-99)[F 91 ]MBP 83-99
SEQ ID NO. 15
cyclo(83-99)E N P V V H F F F N I V T P R T P
cyclo(83-99)[Y 91 ]MBP 83-99
SEQ ID NO. 16
cyclo(83-99)E N P V V H F F Y N I V T P R T P
cyclo(83-99)[E 91 ]MBP 83-99
SEQ ID NO. 14
cyclo(83-99)E N P V V H F F E N I V T P R T P
cyclo(83-99)[A 91 , A 96 ]MBP 83-99
SEQ ID NO. 13
cyclo(83-99)E N P V V H F F A N I V T A R T P
cyclo(83-99)[R 91 , A 96 ]MBP 83-99
SEQ ID NO. 12
cyclo(83-99)E N P V V H F F R N I V T A R T P
cyclo(83-99)[F 91 , A 96 ]MBP 83-99
SEQ ID NO. 20
cyclo(83-99)E N P V V H F F F N I V T A R T P
cyclo(83-99)[Y 91 , A 96 ]MBP 83-99
SEQ ID NO. 21
cyclo(83-99)E N P V V H F F Y N I V T A R T P
cyclo(83-99)[S 91 , A 96 ]MBP 83-99
SEQ ID NO. 22
cyclo(83-99)E N P V V H F F S N I V T A R T P.Cited by (0)
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