US2014065126A1PendingUtilityA1
BChE ALBUMIN FUSIONS FOR THE TREATMENT OF COCAINE ABUSE
Est. expiryDec 8, 2029(~3.4 yrs left)· nominal 20-yr term from priority
Inventors:Liora Sklair-TavronMoti RosenstockLiron Shemesh-DarvishHussein HallakVictor PiryatinskyViktor RoschkeDavid Lafleur
C07K 14/765C07K 14/001A61P 25/30A61P 25/36C07K 2319/31C12Y 301/01084C12N 9/18A61K 38/00
40
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Claims
Abstract
A method of attenuating a biological effect of cocaine exposure in a primate. Such method includes administering to the primate an amount of a BChE-albumin fusion protein comprising the amino acid substitutions A227S, S315G, A356W, and Y360G, wherein the amount of the fusion protein is effective to cause attenuation of the biological effect of cocaine exposure in the primate.
Claims
exact text as granted — not AI-modified1 . A method of attenuating a biological effect of a cocaine exposure in a primate comprising administering to the primate an amount of a fusion protein comprising:
(a) a mutant butyrylcholinesterase (BChE) polypeptide comprising the sequence
(SEQ ID NO: 1)
EDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLT
KWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIP
APKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGA
LGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESSG
AASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLT
GCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLGVNFGPTVDGDFLT
DMPDILLELGQFKKTQILVGVNKDEGTWFLVGGAPGFSKDNNSIITRKEF
QEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFIC
PALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPL
ERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKY
LTLNTESTRIMTKLRAQQCRFWTSFFPKV,
(b) a human serum albumin (HSA) polypeptide comprising the sequence
(SEQ ID NO: 2)
DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFA
KTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNE
CFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFY
APELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKC
ASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDL
LECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPA
DLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLA
KTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGE
YKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAE
DYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPK
EFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDD
FAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL,
and
(c) a signal peptide comprising the sequence MRPTWAWWLFLVLLLALWAPARG (SEQ ID NO:3),
wherein the amount of the fusion protein is effective to cause attenuation of the biological effect of the cocaine exposure in the primate.
2 . The method of claim 1 , wherein the fusion protein comprises the sequence
(SEQ ID NO: 4)
MRPTWAWWLFLVLLLALWAPARGEDDIIIATKNGKVRGMNLTVFGGTVTA
FLGIPYAQPPLGRLRFKKPQSLTKWSDIWNATKYANSCCQNIDQSFPGFH
GSEMWNPNTDLSEDCLYLNVWIPAPKPKNATVLIWIYGGGFQTGTSSLHV
YDGKFLARVERVIVVSMNYRVGALGFLALPGNPEAPGNMGLFDQQLALQW
VQKNIAAFGGNPKSVTLFGESSGAASVSLHLLSPGSHSLFTRAILQSGSF
NAPWAVTSLYEARNRTLNLAKLTGCSRENETEIIKCLRNKDPQEILLNEA
FVVPYGTPLGVNFGPTVDGDFLTDMPDILLELGQFKKTQILVGVNKDEGT
WFLVGGAPGFSKDNNSIITRKEFQEGLKIFFPGVSEFGKESILFHYTDWV
DDQRPENYREALGDVVGDYNFICPALEFTKKFSEWGNNAFFYYFEHRSSK
LPWPEWMGVMHGYEIEFVFGLPLERRDNYTKAEEILSRSIVKRWANFAKY
GNPNETQNNSTSWPVFKSTEQKYLTLNTESTRIMTKLRAQQCRFWTSFFP
KVDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTE
FAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPER
NECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPY
FYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRL
KCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHG
DLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEM
PADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLR
LAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQL
GEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPC
AEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYV
PKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVM
DDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL.
3 - 45 . (canceled)
46 . A method of attenuating a biological effect of a cocaine exposure in a primate comprising administering to the primate an amount of a fusion protein comprising:
(a) a mutant butyrylcholinesterase (BChE) polypeptide comprising the sequence
(SEQ ID NO: 1)
EDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLT
KWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIP
APKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGA
LGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESSG
AASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLT
GCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLGVNFGPTVDGDFLT
DMPDILLELGQFKKTQILVGVNKDEGTWFLVGGAPGFSKDNNSIITRKEF
QEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFIC
PALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPL
ERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKY
LTLNTESTRIMTKLRAQQCRFWTSFFPKV,
and
(b) a human serum albumin (HSA) polypeptide comprising the sequence
(SEQ ID NO: 2)
DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFA
KTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNE
CFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFY
APELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKC
ASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDL
LECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPA
DLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLA
KTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGE
YKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAE
DYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPK
EFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDD
FAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL,
wherein the amount of the fusion protein is effective to cause attenuation of the biological effect of the cocaine exposure in the primate.
47 . The method of claim 46 , wherein the fusion protein comprises the sequence
(Residues 24 to 1137 of SEQ ID NO: 4)
EDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLT
KWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIP
APKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGA
LGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESSG
AASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLT
GCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLGVNFGPTVDGDFLT
DMPDILLELGQFKKTQILVGVNKDEGTWFLVGGAPGFSKDNNSIITRKEF
QEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFIC
PALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPL
ERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKY
LTLNTESTRIMTKLRAQQCRFWTSFFPKVDAHKSEVAHRFKDLGEENFKA
LVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFG
DKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVD
VMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQA
ADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQ
RFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSI
SSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESEDVCKNYAE
AKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYA
KVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTP
TLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSD
RVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKER
QIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEE
GKKLVAASQAALGL.
48 . The method of claim 46 , wherein the fusion protein is administered by intramuscular injection.
49 . A pharmaceutical composition comprising:
(I) a fusion protein comprising: (a) a mutant butyrylcholinesterase (BChE) polypeptide comprising the sequence
(SEQ ID NO: 1)
EDDIIIATKNGKVRGMNLTVFGGTVTAFLGIPYAQPPLGRLRFKKPQSLT
KWSDIWNATKYANSCCQNIDQSFPGFHGSEMWNPNTDLSEDCLYLNVWIP
APKPKNATVLIWIYGGGFQTGTSSLHVYDGKFLARVERVIVVSMNYRVGA
LGFLALPGNPEAPGNMGLFDQQLALQWVQKNIAAFGGNPKSVTLFGESSG
AASVSLHLLSPGSHSLFTRAILQSGSFNAPWAVTSLYEARNRTLNLAKLT
GCSRENETEIIKCLRNKDPQEILLNEAFVVPYGTPLGVNFGPTVDGDFLT
DMPDILLELGQFKKTQILVGVNKDEGTWFLVGGAPGFSKDNNSIITRKEF
QEGLKIFFPGVSEFGKESILFHYTDWVDDQRPENYREALGDVVGDYNFIC
PALEFTKKFSEWGNNAFFYYFEHRSSKLPWPEWMGVMHGYEIEFVFGLPL
ERRDNYTKAEEILSRSIVKRWANFAKYGNPNETQNNSTSWPVFKSTEQKY
LTLNTESTRIMTKLRAQQCRFWTSFFPKV,
and
(b) a human serum albumin (HSA) polypeptide comprising the sequence
(SEQ ID NO: 2)
DAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFA
KTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNE
CFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFY
APELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKC
ASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDL
LECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPA
DLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLA
KTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGE
YKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAE
DYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPK
EFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDD
FAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL,
and
(II) a formulation buffer comprising 10 mM sodium phosphate, 200 mM mannitol, 60 mM trehalose, and 0.01% (w/v) polysorbate 80, pH 7.2.Join the waitlist — get patent alerts
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