US 7,118,872 B2Granted

Binding polypeptides for B lymphocyte stimulator protein (BLyS)

AssigneeDyax Corp.

InventorsJames P. Beltzer, Tony J. Fleming, Robert Charles Ladner

Life of this patent

Estimating the term…

Abstract

Binding polypeptides comprising specific amino acid sequences are disclosed that bind B Lymphocyte Stimulator (BLyS) protein or BLyS-like polypeptides. The binding polypeptides can be used in methods of the invention for detecting or isolating BLyS protein or BLyS-like polypeptides in solutions or mixtures, such as blood, tissue samples, or conditioned media.

Claims31

Dependent claims

A B lymphocyte stimulator protein (BLyS) binding polypeptide comprising an amino acid sequence of the following formula:

Cys-X5-Phe-X7-Trp-Glu-Cys (residue 4–10 of SEQ ID NO:1), (H)
wherein
X5 is Phe, Trp, or Tyr;
and
X7 is Pro or Tyr;
or
Cys-X2-X3-X4-X5-X6-X7-Cys (SEQ ID NO:9), (I)
wherein
X2 is Asp, Ile, Leu, or Tyr;
X3 is Arg, Asp, Glu, His, Ile, Leu, Lys, Phe, Pro, Tyr, or Val;
X4 is His, Leu, Lys, or Phe;
X5 is Leu, Pro, or Thr;
X6 is Arg, Asn, Gly, His, Ile, Lys, Met, or Trp;
and
X7 is Ala, Asn, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Ser, Trp, Tyr, or Val;
or
Cys-X2-X3-X4-X5-X6-X7-X8-Cys (SEQ ID NO:10), (J)
wherein
X2 is Asn, or Asp;
X3 is Arg, Asp, Ile, Leu, Met, Pro, or Val;
X4 is Ala, Ile, Leu, Pro, Thr, or Val;
X5 is Asn, His, Ile, Leu, Lys, Phe, or Thr;
X6 is Asn, Glu, Gly, His, Leu, Lys, Met, Pro, or Thr;
X7 is Arg, Asn, Asp, Gln, Glu, Gly, Ile, Lys, Met, Pro, Ser, or Trp;
and
X8 is Arg, Glu, Gly, Lys, Phe, Ser, Trp, or Tyr;
or
Cys-X2-X3-X4-X5-X6-X7-X8-X9-Cys (SEQ ID NO:11), (K)
wherein
X2 is Asp, Gln, His, Ile, Leu, Lys, Met, Phe, or Thr;
X3 is His, Ile, Leu, Met, Phe, Pro, Trp, or Tyr;
X4 is Asp, His, Leu, or Ser;
X5 is Ala, Arg, Asp, Glu, Leu, Phe, Pro, or Thr;
X6 is Ala, Arg, Asn, or Leu;
X7 is Ile, Leu, Met, Pro, Ser, or Thr;
X8 is Ala, Arg, Asn, Gly, His, Lys, Ser, or Tyr;
and
X9 is Ala, Arg, Asn, Gln, Leu, Met, Ser, Trp, Tyr, or Val;
or
Cys-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-Cys (SEQ ID NO:12), (L)
wherein
X2 is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val;
X3 is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr;
X4 is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr;
X5 is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr;
X6 is Asp, Leu, Pro, Thr, or Val;
X7 is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr;
X8 is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr;
X9 is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr;
X10 is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr;
and
X11 is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val.

49 more elements

A BLyS binding polypeptide comprising an amino acid sequence of the following formula:

(A) X1-X2-X3-Cys-X5-Phe-X7-Trp-Glu-Cys-X11-X12-X13 (SEQ ID NO:1), (A)
wherein
X1 is Ala, Asn, Lys, or Ser;
X2 is Ala, Glu, Met, Ser, or Val;
X3 is Ala, Asn, Lys, or Pro;
X5 is Phe, Trp, or Tyr;
X7 is Pro or Tyr;
X11 is Ala, Gln, His, Phe, or Val;
X12 is Asn, Gln, Gly, His, Ser, or Val;
and
X13 is Ala, Asn, Gly, Ile, Pro, or Ser;
or
X1-X2-X3-Cys-X5-X6-X7-X8-X9-X10-Cys-X12-X13-X14 (SEQ ID NO:2), (B)
wherein
X1 is Ala, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, or is absent;
X2 is Ala, Asn, Asp, Gln, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val;
X3 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val;
X5 is Asp, Ile, Leu, or Tyr;
X6 is Arg, Asp, Glu, His, Ile, Leu, Lys, Phe, Pro, Tyr, or Val;
X7 is His, Leu, Lys, or Phe;
X8 is Leu, Pro, or Thr;
X9 is Arg, Asn, Gly, His, Ile, Lys, Met, or Trp;
X10 is Ala, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Ser, Trp, Tyr, or Val;
X12 is Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Ser, Trp, Tyr, or Val;
X13 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val;
and
X14 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Phe, Pro, Trp, Tyr, Val, or is absent;
or
X1-X2-X3-Cys-X5-X6-X7-X8-X9-X10-X11-Cys-X13-X14-X15 (SEQ ID NO:3), (C)
wherein
X1 is Ala, Arg, Asn, Asp, Leu, Lys, Phe, Pro, Ser, or Thr;
X2 is Asn, Asp, Gln, His, Ile, Lys, Pro, Thr, or Trp;
X3 is Ala, Arg, Asn, Gln, Glu, His, Phe, Pro, or Thr;
X5 is Asn, Asp, Pro, Ser, or Thr;
X6 is Arg, Asp, Ile, Leu, Met, Pro, or Val;
X7 is Ala, Ile, Leu, Pro, Thr, or Val;
X8 is Asn, His, Ile, Leu, Lys, Phe, or Thr;
X9 is Asn, Glu, Gly, His, Leu, Lys, Met, Pro, or Thr;
X10 is Arg, Asn, Asp, Gln, Glu, Gly, Ile, Lys, Met, Pro, Ser, or Trp;
X11 is Arg, Glu, Gly, Lys, Phe, Ser, Trp, or Tyr;
X13 is Gln, Glu, Ile, Leu, Phe, Pro, Ser, Tyr, or Val;
X14 is Asn, Gly, Ile, Phe, Pro, Thr, Trp, or Tyr;
and
X15 is Asn, Asp, Glu, Leu, Lys, Met, Pro, or Thr;
or
X1-X2-X3-Cys-X5-X6-X7-X8-X9-X10-X11-X12-Cys-X14-X15-X16 (SEQ ID NO:4), (D)
wherein
X1 is Asn, Asp, His, Leu, Phe, Pro, Ser, Tyr, or is absent;
X2 is Arg, Asn, Asp, His, Phe, Ser, or Trp;
X3 is Asn, Asp, Leu, Pro, Ser, or Val;
X5 is Asp, Gln, His, Ile, Leu, Lys, Met, Phe, or Thr;
X6 is His, Ile, Leu, Met, Phe, Pro, Trp, or Tyr;
X7 is Asp, His, Leu, or Ser;
X8 is Ala, Arg, Asp, Glu, Leu, Phe, Pro, or Thr;
X9 is Ala, Arg, Asn, or Leu;
X10 is Ile, Leu, Met, Pro, Ser, or Thr;
X11 is Ala, Arg, Asn, Gly, His, Lys, Ser, or Tyr;
X12 is Ala, Arg, Asn, Gln, Leu, Met, Ser, Trp, Tyr, or Val;
X14 is Asp, Gly, Leu, Phe, Tyr, or Val;
and
X15 is Asn, His, Leu, Pro, or Tyr;
and X16 is Asn, Asp, His, Phe, Ser, or Tyr;
or
X1-X2-X3-Cys-X5-X6-X7-X8-X9-X10-X11-X12-X13-X14-Cys-X16-X17-X18 (SEQ ID NO:5), (E)
wherein
X1 is Arg, Asp, Gly, His, Leu, Phe, Pro, Ser, Trp, Tyr, or is absent;
X2 is Ala, Arg, Asn, Asp, Gly, Pro, Ser, or is absent;
X3 is Arg, Asn, Gln, Glu, Gly, Lys, Met, Pro, Trp or Val;
X5 is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val;
X6 is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr;
X7 is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr;
X8 is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr;
X9 is Asp, Leu, Pro, Thr, or Val;
X10 is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr;
X11 is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr;
X12 is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr;
X13 is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr;
X14 is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val;
X16 is Arg, Asp, Gly, His, Lys, Met, Phe, Pro, Ser, or Trp;
X17 is Arg, Asn, Asp, Gly, His, Phe, Pro, Ser, Trp or Tyr;
and
X18 is Ala, Arg, Asn, Asp, His, Leu, Phe, or Trp;
or
X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12 (SEQ ID NO:6), (F)
wherein
X1 is Ala, Arg, Gly, His, Leu, Lys, Met, Phe, Trp, Tyr, or Val;
X2 is Ala, Arg, Gln, His, Ile, Leu, Phe, Thr, Trp, or Tyr;
X3 is Ala, Asp, Lys, Phe, Thr, Trp or Tyr;
X4 is Arg, Asp, Gln, Lys, Met, Phe, Pro, Ser, Tyr, or Val;
X5 is Asp, Leu, Lys, Phe, Pro, Ser, or Val;
X6 is His, Ile, Leu, Pro, Ser, or Thr;
X7 is Arg, Gly, His, Leu, Lys, Met, or Thr;
X8 is Ala, Arg, Asn, Ile, Leu, Lys, Met, or Thr;
X9 is Ala, Asn, Arg, Asp, Glu, Gly, His, Leu, Met, Ser, Trp, Tyr, or Val;
X10 is Ile, Leu, Phe, Ser, Thr, Trp, Tyr, or Val;
X11 is Ala, Arg, Gly, His, Ile, Leu, Lys, Pro, Ser, Thr, Trp, Tyr, or Val;
and
X12 is Arg, Asp, His, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val;
or
X1-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-X12-X13 (SEQ ID NO:7), (G)
wherein
X1 is Asp, Gln, Glu, Gly, His, Lys, Met, or Trp;
X2 is Arg, Gln, His, Ile, Leu, or Pro;
X3 is Asp, Gly, Ile, Lys, Thr, Tyr or Val;
X4 is Asn, Asp, Gln, Glu, Met, Pro, Ser, or Tyr;
X5 is Asn, Asp, His, Ile, Leu, Met, Pro, Thr or Val;
X6 is Asp, Glu, His, Leu, Lys, Pro, or Val;
X7 is Arg, Asn, Gln, His, Ile, Leu, Met, Pro, or Thr;
X8 is Gln, Gly, His, Leu, Met, Ser, or Thr;
X9 is Asn, Gln, Gly, His, Leu, Lys, Ser, or Thr;
X10 is Ala, Gly, Ile, Leu, Lys, Met, or Phe;
X11 is Ala, Glu, His, Ile, Leu, Met, Ser, Thr, Trp, Tyr, or Val;
X12 is Arg, Gln, Glu, Gly, His, Ile, Lys, Tyr, or Val;
and
X13 is Arg, Asn, Glu, His, Ile, Ser, Thr, Trp, or Val.

112 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/932,322Filed 17 Aug 2001 · us provisional application
Priority: 18 Aug 2000
Published: US 2003/0194743 A116 Oct 2003
Granted: 10 Oct 2006
Term ends: Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07K 14/705
From animals; from humans: receptors; Cell surface antigens; Cell surface determinants
C07K 1/047
On carriers: simultaneous synthesis of different peptide species; Peptide libraries
C07K 5/1021
Tetrapeptides: with the first amino acid being acidic
C07K 7/06
Linear peptides containing only normal peptide links: having 5 to 11 amino acids

Family

Application60/226,489Us provisional application · filed 18 Aug 2000
US 2003/0194743 A1Pre-grant publication · published 16 Oct 2003
US 7,118,872 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A B lymphocyte stimulator protein (BLyS) binding polypeptide comprising an amino acid sequence of the following formula:

Cys-X5-Phe-X7-Trp-Glu-Cys (residue 4–10 of SEQ ID NO:1), (H)
wherein
X5 is Phe, Trp, or Tyr;
and
X7 is Pro or Tyr;
or
Cys-X2-X3-X4-X5-X6-X7-Cys (SEQ ID NO:9), (I)
wherein
X2 is Asp, Ile, Leu, or Tyr;
X3 is Arg, Asp, Glu, His, Ile, Leu, Lys, Phe, Pro, Tyr, or Val;
X4 is His, Leu, Lys, or Phe;
X5 is Leu, Pro, or Thr;
X6 is Arg, Asn, Gly, His, Ile, Lys, Met, or Trp;
and
X7 is Ala, Asn, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Ser, Trp, Tyr, or Val;
or
Cys-X2-X3-X4-X5-X6-X7-X8-Cys (SEQ ID NO:10), (J)
wherein
X2 is Asn, or Asp;
X3 is Arg, Asp, Ile, Leu, Met, Pro, or Val;
X4 is Ala, Ile, Leu, Pro, Thr, or Val;
X5 is Asn, His, Ile, Leu, Lys, Phe, or Thr;
X6 is Asn, Glu, Gly, His, Leu, Lys, Met, Pro, or Thr;
X7 is Arg, Asn, Asp, Gln, Glu, Gly, Ile, Lys, Met, Pro, Ser, or Trp;
and
X8 is Arg, Glu, Gly, Lys, Phe, Ser, Trp, or Tyr;
or
Cys-X2-X3-X4-X5-X6-X7-X8-X9-Cys (SEQ ID NO:11), (K)
wherein
X2 is Asp, Gln, His, Ile, Leu, Lys, Met, Phe, or Thr;
X3 is His, Ile, Leu, Met, Phe, Pro, Trp, or Tyr;
X4 is Asp, His, Leu, or Ser;
X5 is Ala, Arg, Asp, Glu, Leu, Phe, Pro, or Thr;
X6 is Ala, Arg, Asn, or Leu;
X7 is Ile, Leu, Met, Pro, Ser, or Thr;
X8 is Ala, Arg, Asn, Gly, His, Lys, Ser, or Tyr;
and
X9 is Ala, Arg, Asn, Gln, Leu, Met, Ser, Trp, Tyr, or Val;
or
Cys-X2-X3-X4-X5-X6-X7-X8-X9-X10-X11-Cys (SEQ ID NO:12), (L)
wherein
X2 is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val;
X3 is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr;
X4 is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr;
X5 is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr;
X6 is Asp, Leu, Pro, Thr, or Val;
X7 is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr;
X8 is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr;
X9 is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr;
X10 is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr;
and
X11 is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val.

49 more elements

Facts

Application

09/932,322Filed 17 Aug 2001 · us provisional application

Priority

18 Aug 2000

Published

US 2003/0194743 A116 Oct 2003

Granted

10 Oct 2006

Term ends

Not estimatedThe source records don’t support an estimate.

Classification8 codes

C07K 14/705
From animals; from humans: receptors; Cell surface antigens; Cell surface determinants
C07K 1/047
On carriers: simultaneous synthesis of different peptide species; Peptide libraries
C07K 5/1021
Tetrapeptides: with the first amino acid being acidic
C07K 7/06
Linear peptides containing only normal peptide links: having 5 to 11 amino acids