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US 2003/0199013 A1Published application
Fragments of prion proteins
AssigneeProteus Molecular Design Limited
InventorsRobert Vincent Fishleigh, Barry Robson, Roger Paul Mee
Life of this patent
Estimating the term…
Abstract
Synthetic polypeptides having at least one antigenic site of a prior protein, methods for their use and manufacture, antibodies raised against such polypeptides and diagnostic kits containing these polypeptides or antibodies.
Claims45
A synthetic polypeptide having at least one antigenic site of a prion protein, wherein the polypeptide is selected from the group consisting of polypeptides of Formulae I, II, III, IV, VI, VII, VIIIa, VIIIb and IX, or has one of the following sequences:
- 46 (Formula I (SEQ ID NO:52)) X-(R1-Lys-His-R2)-Ala-Gly-Ala-Ala-Ala-R3-Gly-Ala- Val-Val-Gly-Gly-Leu-Gly-Gly-Tyr-Met-Leu-Gly-Ser- Ala-Met-Ser-(Arg-Pro-R4-R5)-Y
- wherein R1 is an amino acid residue selected from Met, Leu and Phe;
- R2 is either Met or Val;
- R3 is Ala or is absent;
- R4 and R5 are independently an amino acid residue selected from Leu, Ile and Met;
- 47 (Formula II (SEQ ID NO:53)) X-(Ser-Ala-Met-Ser)-Arg-Pro-R4-R5-His-Phe-Gly-R6- Asp-R7-Glu-Asp-Arg-Tyr-Tyr-Arg-Glu-Asn-Met-R8-Arg- (Tyr-Pro-Asn-Gln)-Y
- wherein R4 and R5 are the same as in Formula I;
- R6 is either Asn or Ser;
- R7 is either Tyr or Trp;
- R8 is an amino acid residue selected from His, Tyr and Asn;
- 48 (Formula III (SEQ ID NO:54)) X-(Asn-Met-R8-Arg)-Tyr-Pro-Asn-Gln-val-Tyr-Tyr- Arg-Pro-R9-Asp-R10-Tyr-R11-Asn-Gln-Asn-Asn-Phe-Val- His-(Asp-Cys-Val-Asn)-Y
- wherein R8 is an amino acid residue selected from His, Tyr and Asn;
- R9 is Val or Met;
- R10 is an amino acid residue selected from Gln, Glu and Arg;
- R11 is Ser or Asn;
- 49 (Formula IV (SEQ ID NO:55)) X-(Tyr-Tyr-R12-R13-Arg)-R14-R15-Ser-R16-R17-R18- Leu-Phe-Ser-Ser-Pro-Pro-Val-Ile-Leu-Leu-Ile-Ser- Phe-Leu-Ile-Phe-Leu-R19-Val-Gly-Y
- wherein R12 is Asp or Gln;
- R13 is Gly or absent;
- R14 is Gly or Arg;
- R15 is Ala or Ser;
- R16 is Ser or absent;
- R17 is an amino acid residue selected from Ala, Thr, Met and Val;
- R18 is Val or Ile;
- R19 is Ile or Met;
- 50 (Formula VI (SEQ ID NO:59)) X-(R31-R32-Trp-R33)-Trp-Leu-Gly-R34-R35-R36-Trp- R37(Trp-Leu-Gly-R38)-Y
- wherein R31 and R35 are each independently either Ala or Thr;
- R32 and R36 are each independently an amino acid residue selected from Ser, Pro and Thr;
- R33 and R37 are each independently either Trp or Arg;
- R34 and R38 are each independently an amino acid residue selected from Ala, Ser, Pro and Thr;
- 51 (Formula VII (SEQ ID NO:60)) X-(R39-R40-Met-R41)-Val-Ala-Gly-R42-R43-R44-Met-R45- (Val-Ala-Gly-R46)-Y
- wherein R39 and R43 are each independently either Ser or Asn;
- R40 and R44 are each independently an amino acid residue selected from Pro, Leu and His,
- R41 and R45 are each independently Val or Glu;
- R42 and R46 are each independently selected from Val, Ala, Asp and Gly;
- 52 (Formula VIIIa (SEQ ID NO:61)) X-(Asn-Phe-Val-His)-Asp-Cys-Val-Asn-Ile-Thr-R47- Lys-R48-His-Thr-Val-R49-Thr-Thr-Thr-Lys-Gly-Glu- Asn-Phe-Thr-Glu-(Thr-Asp-R50-Lys)-Y
- wherein R47 is either Ile or Val;
- R48 is either Gln or Glu;
- R49 is either Val or Thr;
- R50 is either Val or Ile;
- 53 (Formula VIIIb (SEQ ID NO:62)) X-(Met-Cys-R51-Thr)-Gln-Tyr-R52-R53-Glu-Ser-Gln- Ala-Tyr-Tyr-R54-R55-Arg-(R56-R57-Ser-R58-R59)-Y
- wherein R51 is an amino acid residue selected from Ile, Thr and Val;
- R52 is either Gln or Glu;
- R53 is either Arg or Lys;
- R54 is either Asp or Gln;
- R55 is Gly or is absent;
- R56 is either Gly or Arg;
- R57 is either Ala or Ser;
- R58 is Ser or absent;
- R59 is an amino acid residue selected from Ala, Thr, Met and Val;
- wherein one or more residues within the parentheses are present or absent with the proviso that if they are present they are attached to the rest of the peptide in sequence;
- and
- X and Y are each independently absent or one or more additional amino acid residues, with the proviso that when present neither X nor Y provide or form part of an antigenic property of the prion protein which, in the corresponding portion of sequence of a natural prion protein, is contiguous with the sequence to which X and Y are attached;
- or
- [La−F]m−[Lb−G]n−Lc (Formula IX)
- wherein F and G are each independently a polypeptide according to any one of Formulae I to IV and VI to VIIIb, L is a linking sequence, a, b and c are each independently 0 or 1, and m and n are each positive numbers, or F and G are each independently a subfragment of such sequence.
52 more elements
Dependencies are inferred from the claim text.