US2016024155A1PendingUtilityA1
Polypeptides for treating and/or limiting influenza infection
Assignee: UNIV WASHINGTON CT COMMERCIALIPriority: Aug 3, 2010Filed: Oct 7, 2015Published: Jan 28, 2016
Est. expiryAug 3, 2030(~4 yrs left)· nominal 20-yr term from priority
C07K 7/08C07K 14/00C07K 14/001A61P 31/16G01N 33/53A61K 38/10A61K 38/16A61K 38/00G01N 33/56983G01N 2333/11G01N 2469/10
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Claims
Abstract
Polypeptides are disclosed herein, which recognize and are strong binders to Influenza A hemagglutinin and can be used, for example, to treat and/or limit development of an influenza infection.
Claims
exact text as granted — not AI-modifiedWe claim:
1 . A polypeptide comprising an amino acid sequence according to general formula II
R1-R2-R3-R4-R5-R6-R7-R8-R9-Ala-R10-R11-Phe (SEQ ID NO: 83), wherein R1 is selected from the group consisting of Phe and Val; R2 is selected from the group consisting of Ser, Ala, Phe, Gly, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Thr, and Val; R3 is selected from the group consisting of Glu, and Asp; R4 is selected from the group consisting of Asn, His, Ile, Lys, Leu, Met, Arg, Ser, and Thr; R5 is selected from the group consisting of Leu, Phe, Ile, Met, Asn, Gln, and Val; R6 is selected from the group consisting of Ala, Asp, Lys, Met, Asn, Gln, Arg, Glu, and Val; R7 is selected from the group consisting of Phe, Asp, Asn, and Tyr; R8 is selected from the group consisting of Glu, Ala, Asp, Gly, His, Lys, Leu, Met, Asn, Gln, Arg, Ser, Thr, Val, and Tip; R9 is selected from the group consisting of Leu, Phe, Ile, Met, and Val; R10 is selected from the group consisting of Leu, Ile, Met, and Tyr; and R11 is selected from the group consisting of Ser, Ala, Gly, and Tyr;
2 . The polypeptide of claim 1 , wherein general formula II is
(SEQ ID NO: 84)
R1-R2-R3-R4-R5-R6-R7-R8-R9-Ala-R10-R11-Phe-X1-R12-
R13-X2-R14,
wherein
X1 is 5-15 amino acids in length, wherein each position can be any amino acid;
R12 is selected from the group consisting of Gln, Tyr, Phe, Met, Arg, Lys, and Gly;
R13 is selected from the group consisting of Tyr, Asp, Met, Asn, and Ser;
X2 is any amino acid; and
R14 is selected from the group consisting of Ser, Arg, and Lys.
3 . The polypeptide of claim 2 , wherein X1 comprises the amino acid sequence TNKDTPDRW-Z1-KVA (SEQ ID NO: 85) where Z1 is Ala, Lys, Arg, Gly, or Thr.
4 . The polypeptide of claim 2 , wherein general formula II is A1-R1-R2-R3-R4-R5-R6-R7-R8-R9-Ala-R10-R11-Phe-X1-R12-R13-X2-R14-B1 (SEQ ID NO: 86), wherein one or both of A1 and B1 are present, and wherein:
A1 comprises the amino acid sequence: Z2-ASTRGSGRPW-Z3 (SEQ ID NO: 87), wherein Z2 is absent or is Met, and Z3 is selected from group consisting of Gly, Arg, Lys, Asp and B1 comprises the amino acid sequence G-Z4-TPEEVKKHYE (SEQ ID NO: 88), where Z4 is R or K.
5 . The polypeptide of claim 1 , comprising a polypeptide selected from the group consisting of
(SEQ ID NO: 90)
FSENLAFELALA;
>HB80.3_s4_E81:
(SEQ ID NO: 91)
FSENVAFEIALSF;
>HB80.3_s4_E83:
(SEQ ID NO: 93)
FRENIAFEIALYF;
>HB80.3_s4_E85:
(SEQ ID NO: 95)
FSENIAFELALYF;
>HB80.3_s4_E86:
(SEQ ID NO: 96)
FSENVAFELALYF;
>HB80.3_s4_E88:
(SEQ ID NO: 98)
FKENLEFEIALSF;
>HB80.3_s4_E99:
(SEQ ID NO: 109)
FSENLAFELALYF;
and
>HB80.3_02:
(SEQ ID NO: 113)
FSENIAFEIALSF.
6 . The polypeptide of claim 1 , comprising a polypeptide selected from the group consisting of
>HB80.3
(SEQ ID NO: 115)
FSENLAFELALSFTNKDTPDRWAKVAQYVS;
>HB80.3_s4_E81:
(SEQ ID NO: 116)
FSENVAFEIALSFTNKDTPDRWKKVARYVR;
>HB80.3_s4_E82:
(SEQ ID NO: 117)
FSENVAFEIALSFTNKDTPDRWAKVARYVR;
>HB80.3_s4_E83:
(SEQ ID NO: 118)
FRENIAFEIALYFTNKDTPDRWRKVARYVK;
>HB80.3_s4_E84:
(SEQ ID NO: 119)
FSENVAFEIALSFTNKDTPDRWRKVARYVR;
>HB80.3_s4_E85:
(SEQ ID NO: 120)
FSENIAFELALYFTNKDTPDRWGKVARYVR;
>HB80.3_s4_E86:
(SEQ ID NO: 121)
FSENVAFELALYFTNKDTPDRWKKVARYVK;
>HB80.3_s4_E87:
(SEQ ID NO: 122)
FSENIAFELALYFTNKDTPDRWKKVARYVK;
>HB80.3_s4_E88:
(SEQ ID NO: 123)
FKENLEFEIALSFTNKDTPDRWKKVAYYVR;
>HB80.3_s4_E90:
(SEQ ID NO: 125)
FSENVAFELALYFTNKDTPDRWTKVARYVK;
>HB80.3_s4_E93:
(SEQ ID NO: 128)
FSENVAFELALYFTNKDTPDRWGKVAQYVR;
>HB80.3_s4_E94:
(SEQ ID NO: 129)
FSENVAFELALYFTNKDTPDRWAKVARYVK;
>HB80.3_s4_E96:
(SEQ ID NO: 131)
FSENVAFEIALSFTNKDTPDRWRKVAYYVR;
>HB80.3_s4_E99:
(SEQ ID NO: 134)
FSENLAFELALYFTNKDTPDRWAKVAYYVK;
>HB80.3_s4_E100:
(SEQ ID NO: 135)
FSENVAFEIALSFTNKDTPDRWKKVARYVK;
and
>HB80.3_02:
(SEQ ID NO: 138)
FSENIAFEIALSFTNKDTPDRWKKVAQYVK.
7 . The polypeptide of claim 1 , comprising a polypeptide selected from the group consisting of:
(SEQ ID NO: 141)
FAENLAFELALSF;
(SEQ ID NO: 142)
FGENLAFELALSF;
(SEQ ID NO: 143)
FIENLAFELALSF;
(SEQ ID NO: 144)
FKENLAFELALSF;
(SEQ ID NO: 145)
FRENLAFELALSF;
(SEQ ID NO: 146)
FTENLAFELALSF;
(SEQ ID NO: 147)
FVENLAFELALSF;
(SEQ ID NO: 148)
FSENIAFELALSF;
(SEQ ID NO: 149)
FSENVAFELALSF;
(SEQ ID NO: 150)
FSENLKFELALSF;
(SEQ ID NO: 151)
FSENLRFELALSF;
and
(SEQ ID NO: 153)
FSENLAFSLALSF.
(SEQ ID NO: 154)
FSENLAFELALYF.
8 . The polypeptide of claim 1 , comprising a polypeptide selected from the group consisting of:
(SEQ ID NO: 156)
FSENLAFELALSFTNKDTPDRWAKVARYVS;
(SEQ ID NO: 157)
FSENLAFELALSFTNKDTPDRWAKVAYYVS;
(SEQ ID NO: 158)
FSENLAFELALSFTNKDTPDRWAKVAQYVK;
(SEQ ID NO: 159)
FSENLAFELALSFTNKDTPDRWAKVAQYVR;
(SEQ ID NO: 161)
FAENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 162)
FGENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 163)
FIENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 164)
FKENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 165)
FRENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 166)
FTENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 167)
FVENLAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 168)
FSENIAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 169)
FSENVAFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 170)
FSENLKFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 171)
FSENLRFELALSFTNKDTPDRWAKVAQYVS;
(SEQ ID NO: 173)
FSENLAFSLALSFTNKDTPDRWAKVAQYVS;
and
(SEQ ID NO: 174)
FSENLAFELALYFTNKDTPDRWAKVAQYVS.
9 . The polypeptide of claim 1 , comprising a polypeptide selected from the group consisting of:
HB80 Met26Thr
(SEQ ID NO: 180)
MASTRGSGRPWDFSENLAFELALAFTNKDTPDRWANVAQYVSGRTPEEV
KKHYEILVEDIKYIESGKVPFPNYRTTGGNMKTDEKRFRNLKIRLE;
>HB80 Asn36Lys
(SEQ ID NO: 181)
MASTRGSGRPWDFSENLAFELALAFMNKDTPDRWAKVAQYVSGRTPEEVK
KHYEILVEDIKYIESGKVPFPNYRTTGGNMKTDEKRFRNLKIRLE;
>HB80.1 (Met26Thr, Asn36Lys)
(SEQ ID NO: 182)
MASTRGSGRPWDFSENLAFELALAFTNKDTPDRWAKVAQYVSGRTPEEV
KKHYEILVEDIKYIESGKVPFPNYRTTGGNMKTDEKRFRNLKIRLE;
>HB80.2 (Met26Thr, Asn36Lys, Delta54-95)
(SEQ ID NO: 183)
MASTRGSGRPWDFSENLAFELALAFTNKDTPDRWAKVAQYVSGRTPEEVK
KHYE;
>HB80.3 (Aspl2Gly, Ala24Ser, Met26Thr, Asn36Lys,
Delta54-95)
(SEQ ID NO: 184)
MASTRGSGRPWGFSENLAFELALSFTNKDTPDRWAKVAQYVSGRTPEEV
KKHYE;
(SEQ ID NO: 185)
MASTRGSGRPWKFSENLAFELALSFTNKDTPDRWAKVAQYVSGRTPEE
VKKHYE;
(SEQ ID NO: 186)
MASTRGSGRPWRFSENLAFELALSFTNKDTPDRWAKVAQYVSGRTPEE
VKKHYE;
>HB80.3_s4_E81
(SEQ ID NO: 187)
MASTRGSGRPWRFSENVAFEIALSFTNKDTPDRWKKVARYVRGRTPEE
VKKHYE;
>HB80.3_s4_E82
(SEQ ID NO: 188)
MASTRGSGRPWKFSENVAFEIALSFTNKDTPDRWAKVARYVRGRTPEE
VKKHYE;
>HB80.3_s4_E83
(SEQ ID NO: 189)
MASTRGSGRPWGFRENIAFEIALYFTNKDTPDRWRKVARYVKGRTPEE
VKKHYE;
>HB80.3_s4_E84
(SEQ ID NO: 190)
MASTRGSGRPWRFSENVAFEIALSFTNKDTPDRWRKVARYVRGRTPEE
VKKHYE;
>HB80.3_s4_E85
(SEQ ID NO: 191)
MASTRGSGRPWGFSENIAFELALYFTNKDTPDRWGKVARYVRGRTPEE
VKKHYE;
>HB80.3_s4_E86
(SEQ ID NO: 192)
MASTRGSGRPWKFSENVAFELALYFTNKDTPDRWKKVARYVKGRTPE
EVKKHYE;
>HB80.3_s4_E87
(SEQ ID NO: 193)
MASTRGSGRPWKFSENIAFELALYFTNKDTPDRWKKVARYVKGRTPEE
VKKHYE;
>HB80.3_s4_E88
(SEQ ID NO: 194)
MASTRGSGRPWKFKENLEFEIALSFTNKDTPDRWKKVAYYVRGRTPE
EVKKHYE;
>HB80.3_s4_E90
(SEQ ID NO: 196)
MASTRGSGRPWKFSENVAFELALYFTNKDTPDRWTKVARYVKGRTPE
EVKKHYE;
>HB80.3_s4_E92
(SEQ ID NO: 198)
MASTRGSGRPWKFSENVAFEIALSFTNKDTPDRWRKVARYVRGRTPE
EVKKHYE;
>HB80.3_s4_E93
(SEQ ID NO: 199)
MASTRGSGRPWKFSENVAFELALYFTNKDTPDRWGKVAQYVRGRTP
EEVKKHYE;
>HB80.3_s4_E94
(SEQ ID NO: 200)
ASTRGSGRPWKFSENVAFELALYFTNKDTPDRWAKVARYVKGRTPE
EVKKHYE;
>HB80.3_s4_E96
(SEQ ID NO: 202)
MASTRGSGRPWKFSENVAFEIALSFTNKDTPDRWRKVAYYVRGRTP
EEVKKHYE;
>HB80.3_s4_E98
(SEQ ID NO: 204)
MASTRGSGRPWRFSENVAFEIALSFTNKDTPDRWAKVARYVRGRTP
EEVKKHYE;
>HB80.3_s4_E99
(SEQ ID NO: 205)
MASTRGSGRPWKFSENLAFELALYFTNKDTPDRWAKVAYYVKGRTP
EEVKKHYE;
>HB80.3_s4_E100
(SEQ ID NO: 206)
MASTRGSGRPWRFSENVAFEIALSFTNKDTPDRWKKVARYVKGRTP
EEVKKHYE;
>HB80.3_s5_E01
(SEQ ID NO: 207)
MASTKGSGKPWKFSENVAFEIALSFTNKDTPDRWRKVARYVRGKTP
EEVKKHYE;
and
>HB80.3_02
(SEQ ID NO: 209)
MASTRGSGRPWKFSENIAFEIALSFTNKDTPDRWKKVAQYVKGRTPE
EVKKHYE.
10 . The polypeptide of claim 1 , wherein the polypeptide comprises a detectable tag.
11 . An isolated nucleic acid encoding the polypeptide of claim 1 .
12 . A recombinant expression vector comprising the nucleic acid of claim 11 operatively linked to a suitable control sequence.
13 . A recombinant host cell comprising the recombinant expression vector of claim 12 .
14 . A pharmaceutical composition, comprising one or more polypeptides according to claim 1 and a pharmaceutically acceptable carrier.
15 . A method for treating and/or limiting an influenza infection, comprising administering to a subject in need thereof a therapeutically effective amount of one or more polypeptides of claim 1 , or pharmaceutical compositions thereof, to treat and/or limit the influenza infection.
16 . A method for diagnosing an influenza infection, or monitoring progression of an influenza infection, comprising
(a) contacting a biological sample from a subject suspected of having an influenza infection with a diagnostically effective amount of one or more polypeptides of claim 1 under conditions suitable for binding of the polypeptide to a viral HA protein present in the sample; and (b) detecting polypeptide-viral HA binding complexes, where the presence of such binding complexes indicates that the subject has an influenza infection, or provides a measure progression of an influenza infection.Join the waitlist — get patent alerts
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