US2007293434A9PendingUtilityA9
Binding polypeptides and methods based thereon
Est. expiryAug 18, 2020(expired)· nominal 20-yr term from priority
A61P 37/00C07K 14/70578C07K 7/08C07K 14/7151A61K 38/00C07K 2319/00A61K 39/00
56
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Claims
Abstract
Binding polypeptides that specifically bind BLyS protein or BLyS-like polypeptides can be used in methods of the invention for detecting, diagnosing, or prognosing a disease or disorder associated with aberrant BLyS or BLyS receptor expression or inappropriate function of BLyS or BLyS receptor, comprising BLyS binding polypeptides or fragments or variants thereof, that specifically bind to BLyS. The present invention further relates to methods and compositions for preventing, treating or ameliorating a disease or disorder associated with aberrant BLyS or BLyS receptor expression or inappropriate BLyS function or BLyS receptor function, comprising administering to an animal, preferably a human, an effective amount of one or more BLyS binding polypeptides or fragments or variants thereof, that specifically bind to BLyS.
Claims
exact text as granted — not AI-modified1 . A method of treating, preventing or ameliorating a disease or disorder associated with aberrant B Lymphocyte Stimulator (BLyS) or BLyS receptor expression or activity, comprising administering to an animal in which such treatment, prevention or amelioration is desired, a BLyS binding polypeptide in an amount effective to treat, prevent or ameliorate the disease or disorder.
2 . The method of claim 1 , wherein the disease or disorder is an immune system disease or disorder.
3 . The method of claim 2 , wherein the immune system disease or disorder is an autoimmune disease or disorder.
4 . The method of claim 2 , wherein the immune system disease or disorder is an immunodeficiency.
5 . The method of claim 3 , wherein the autoimmune disease or disorder is lupus.
6 . The method of claim 1 , wherein the disease or disorder is glomerular nephritis.
7 . The method of claim 2 , wherein the immune system disease or disorder is rheumatoid arthritis, multiple sclerosis, hypogammaglobulinemia or hypergammaglobulinemia.
8 . The method of claim 2 wherein the immune system disease or disorder is graft vs. host disease.
9 . The method of claim 2 , wherein the immune system disease or disorder is a proliferative disease or disorder.
10 . The method of claim 9 , wherein the proliferative disorder is cancer.
11 . The method of claim 1 , wherein the disease or disorder is an infectious disease or disorder.
12 - 68 . (canceled)
69 . The method according to claim 1 , wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of:
(1)
Asp-Xaa-Leu-Thr,
(SEQ ID NO:446)
wherein Xaa is Pro, Ser, Thr, Phe, Leu, Tyr, Cys, or Ala (preferably Pro or Ser);
(2)
X 1 -X 2 -X 3 -Cys-X 5 -Phe-X 7 -Trp-Glu-Cys-X 11 -X 12 -X 13 ,
(SEQ ID NO:1)
wherein
X 1 is Ala, Asn, Lys, or Ser;
X 2 is Ala, Glu, Met, Ser, or Val;
X 3 is Ala, Asn, Lys, or Pro (preferably Lys);
X 5 is Phe, Trp, or Tyr (preferably Tyr);
X 7 is Pro or Tyr (preferably Pro);
X 11 is Ala, Gln, His, Phe, or Val;
X 12 is Asn, Gln, Gly, His, Ser, or Val; and
X 13 is Ala, Asn, Gly, Ile, Pro, or Ser;
(3)
X 1 -X 2 -X 3 -Cys-X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -Cys-X 12 -X 13 -X 14 ,
(SEQ ID NO:2)
wherein
X 1 is Ala, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val, or is absent;
X 2 is Ala, Asn, Asp, Gln Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val;
X 3 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val (preferably Asp);
X 5 is Asp, Ile, Leu, or Tyr (preferably Asp or Leu);
X 6 is Arg, Asp, Glu, His, Ile, Leu, Lys, Phe, Pro, Tyr, or Val (preferably Glu or Leu);
X 7 is His, Leu, Lys, or Phe (preferably His or Leu);
X 8 is Leu, Pro, or Thr (preferably Thr or Pro);
X 9 is Arg, Asn, Gly, His, Ile, Lys, Met, or Trp (preferably Lys);
X 10 is Ala, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Ser, Trp, Tyr, or Val;
X 12 is Asp, Gln, Glu, Gly, Ile, Leu, Lys, Phe, Ser, Trp, Tyr, or Val;
X 13 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, or Val; and
X 14 is Ala, Arg, Asn, Asp, Gln, Glu, Gly, His, Ile, Leu, Lys, Phe, Pro, Trp, Tyr, Val, or is absent;
(4)
X 1 -X 2 -X 3 -Cys-X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -Cys-X 13 -X 14 -X 15 ,
(SEQ ID NO:3)
wherein
X 1 is Ala, Arg, Asn, Asp, Leu, Lys, Phe, Pro, Ser, or Thr;
X 2 is Asn, Asp, Gln, His, Ile, Lys, Pro, Thr, or Trp;
X 3 is Ala, Arg, Asn, Gln, Glu, His, Phe, Pro, or Thr (preferably Ala);
X 5 is Asn, Asp, Pro, Ser, or Thr (preferably Asp);
X 6 is Arg, Asp, Ile, Leu, Met, Pro, or Val (preferably Ile);
X 7 is Ala, Ile, Leu, Pro, Thr, or Val (preferably Val or Leu);
X 8 is Asn, His, Ile, Leu, Lys, Phe, or Thr (preferably Thr);
X 9 is Asn, Glu, Gly, His, Leu, Lys, Met, Pro, or Thr (preferably Leu);
X 10 is Arg, Asn, Asp, Gln, Glu, Gly, Ile, Lys, Met, Pro, Ser, or Trp;
X 11 is Arg, Glu, Gly, Lys, Phe, Ser, Trp, or Tyr (preferably Ser);
X 13 is Gln, Glu, Ile, Leu, Phe, Pro, Ser, Tyr, or Val (preferably Val);
X 14 is Asn, Gly, Ile, Phe, Pro, Thr, Trp, or Tyr; and
X 15 is Asn, Asp, Glu, Leu, Lys, Met, Pro, or Thr (preferably Glu or Pro);
(5)
X 1 -X 2 -X 3 -Cys-X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -Cys-X 14 -X 15 -X 16 ,
(SEQ ID NO:4)
wherein
X 1 is Asn, Asp, His, Leu, Phe, Pro, Ser, Tyr, or is absent (preferably Ser);
X 2 is Arg, Asn, Asp, His, Phe, Ser, or Trp (preferably Arg);
X 3 is Asn, Asp, Leu, Pro, Ser, or Val (preferably Asn or Asp);
X 5 is Asp, Gln, His, Ile, Leu, Lys, Met, Phe, or Thr;
X 6 is His, Ile, Leu, Met, Phe, Pro, Trp, or Tyr;
X 7 is Asp, His, Leu, or Ser (preferably Asp);
X 8 is Ala, Arg, Asp, Glu, Leu, Phe, Pro, or Thr (preferably Glu or Pro);
X 9 is Ala, Arg, Asn, or Leu (preferably Leu);
X 10 is Ile, Leu, Met, Pro, Ser, or Thr (preferably Thr);
X 11 is Ala, Arg, Asn, Gly, His, Lys, Ser, or Tyr;
X 12 is Ala, Arg, Asn, Gln, Leu, Met, Ser, Trp, Tyr, or Val;
X 14 is Asp, Gly, Leu, Phe, Tyr, or Val (preferably Leu);
X 15 is Asn, His, Leu, Pro, or Tyr (preferably His, Leu or Pro); and
X 16 is Asn, Asp, His, Phe, Ser, or Tyr, (preferably Asp or Ser);
(6)
X 1 -X 2 -X 3 -Cys-X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 -X 14 -Cys-X 16 -X 17 -X 18 ,
(SEQ ID NO:5)
wherein
X 1 is Arg, Asp, Gly, His, Leu, Phe, Pro, Ser, Trp, Tyr, or is absent (preferably Arg);
X 2 is Ala, Arg, Asn, Asp, Gly, Pro, Ser, or is absent (preferably Asn, Asp, Gly, or Pro);
X 3 is Arg, Asn, Gln, Glu, Gly, Lys, Met, Pro, Trp or Val (preferably Gly or Met);
X 5 is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val preferably Trp, Tyr, or Val);
X 6 is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr (preferably Asp);
X 7 is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr (preferably Asp);
X 8 is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr (preferably Leu);
X 9 is Asp, Leu, Pro, Thr, or Val (preferably Leu or Thr);
X 10 is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr (preferably Lys or Thr);
X 11 is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr (preferably Arg or Leu);
X 12 is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr (preferably Thr or Trp);
X 13 is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr (preferably Met or Phe);
X 14 is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val (preferably Val);
X 16 is Arg, Asp, Gly, His, Lys, Met, Phe, Pro, Ser, or Trp (preferably Met);
X 17 is Arg, Asn, Asp, Gly, His, Phe, Pro, Ser, Trp or Tyr, (preferably Arg, His, or Tyr); and
X 18 is Ala, Arg, Asn, Asp, His, Leu, Phe, or Trp (preferably His or Asn);
(7)
X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 ,
(SEQ ID NO:6)
wherein
X 1 is Ala, Arg, Gly, His, Leu, Lys, Met, Phe, Trp, Tyr, or Val (preferably Gly, Tyr, or Val);
X 2 is Ala, Arg, Gln, His, Ile, Leu, Phe, Thr, Trp, or Tyr (preferably His or Tyr);
X 3 is Ala, Asp, Lys, Phe, Thr, Trp or Tyr (preferably Asp or Tyr);
X 4 is Arg, Asp, Gln, Lys, Met, Phe, Pro, Ser, Tyr, or Val (preferably Asp or Gln);
X 5 is Asp, Leu, Lys, Phe, Pro, Ser, or Val (preferably Leu or Ser);
X 6 is His, Ile, Leu, Pro, Ser, or Thr (preferably Leu or Thr);
X 7 is Arg, Gly, His, Leu, Lys, Met, or Thr (preferably Lys or Thr);
X 8 is Ala, Arg, Asn, Ile, Leu, Lys, Met, or Thr (preferably Leu or Lys);
X 9 is Ala, Asn, Arg, Asp, Glu, Gly, His, Leu, Met, Ser, Trp, Tyr, or Val (preferably Met or Ser);
X 10 is Ile, Leu, Phe, Ser, Thr, Trp, Tyr, or Val (preferably Thr or Leu);
X 11 is Ala, Arg, Gly, His, Ile, Leu, Lys, Pro, Ser, Thr, Trp, Tyr, or Val (preferably Pro or Thr); and
X 12 is Arg, Asp, His, Leu, Lys, Met, Phe, Pro, Ser, Trp, Tyr, or Val (preferably Arg or Pro);
(8)
X 1 -X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -X 12 -X 13 ,
(SEQ ID NO:7)
wherein
X 1 is Asp, Gln, Glu, Gly, His, Lys, Met, or Trp (preferably Glu or Lys);
X 2 is Arg, Gln, His, Ile, Leu, or Pro (preferably His or Pro);
X 3 is Asp, Gly, Ile, Lys, Thr, Tyr or Val (preferably Tyr);
X 4 is Asn, Asp, Gln, Glu, Met, Pro, Ser, or Tyr (preferably Asp or Gln);
X 5 is Asn, Asp, His, Ile, Leu, Met, Pro, Thr or Val (preferably Asn or Thr);
X 6 is Asp, Glu, His, Leu, Lys, Pro, or Val (preferably Asp or Pro);
X 7 is Arg, Asn, Gln, His, Ile, Leu, Met, Pro, or Thr (preferably Ile or Pro);
X 8 is Gln, Gly, His, Leu, Met, Ser, or Thr (preferably Leu or Thr);
X 9 is Asn, Gln, Gly, His, Leu, Lys, Ser, or Thr (preferably Lys);
X 10 is Ala, Gly, Ile, Leu, Lys, Met, or Phe (preferably Gly or Met);
X 11 is Ala, Glu, His, Ile, Leu, Met, Ser, Thr, Trp, Tyr, or Val (preferably Ala or Thr);
X 12 is Arg, Gln, Glu, Gly, His, Ile, Lys, Tyr, or Val (preferably Arg or His); and
X 13 is Arg, Asn, Glu, His, Ile, Ser, Thr, Trp, or Val (preferably His);
(9)
Cys-X 2 -Phe-X 4 -Trp-Glu-Cys,
(SEQ ID NO:8)
wherein
X 2 is Phe, Trp, or Tyr (preferably Tyr); and
X 4 is Pro or Tyr (preferably Pro);
(10)
Cys-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -Cys,
(SEQ ID NO:9)
wherein
X 2 is Asp, Ile, Leu, or Tyr (preferably Asp or Leu);
X 3 is Arg, Asp, Glu, His, Ile, Leu, Lys, Phe, Pro, Tyr, or Val (preferably Glu or Leu);
X 4 is His, Leu, Lys, or Phe (preferably His or Leu);
X 5 is Leu, Pro, or Thr (preferably Thr or Pro);
X 6 is Arg, Asn, Gly, His, Ile, Lys, Met, or Trp (preferably Lys); and
X 7 is Ala, Asn, Gln, Glu, Gly, His, Ile, Leu, Met, Phe, Ser, Trp, Tyr, or Val;
(11)
Cys-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -Cys,
(SEQ ID NO:10)
wherein
X 2 is Asn, Asp, Pro, Ser, or Thr (preferably Asp);
X 3 is Arg, Asp, Ile, Leu, Met, Pro, or Val (preferably Ile);
X 4 is Ala, Ile, Leu, Pro, Thr, or Val (preferably Val or Leu);
X 5 is Asn, His, Ile, Leu, Lys, Phe, or Thr (preferably Thr);
X 6 is Asn, Glu, Gly, His, Leu, Lys, Met, Pro, or Thr (preferably Leu);
X 7 is Arg, Asn, Asp, Gln, Glu, Gly, Ile, Lys, Met, Pro, Ser, or Trp;
X 8 is Arg, Glu, Gly, Lys, Phe, Ser, Trp, or Tyr (preferably Ser);
(SEQ ID NO:11)
(12)
Cys-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -Cys,
wherein
X 2 is Asp, Gln, His, Ile, Leu, Lys, Met, Phe, or Thr;
X 3 is His, Ile, Leu, Met, Phe, Pro, Trp, or Tyr;
X 4 is Asp, His, Leu, or Ser (preferably Asp);
X 5 is Ala, Arg, Asp, Glu, Leu, Phe, Pro, or Thr (preferably Glu or Pro);
X 6 is Ala, Arg, Asn, or Leu (preferably Leu);
X 7 is Ile, Leu, Met, Pro, Ser, or Thr (preferably Thr);
X 8 is Ala, Arg, Asn, Gly, His, Lys, Ser, or Tyr;
X 9 is Ala, Arg, Asn, Gln, Leu, Met, Ser, Trp, Tyr, or Val;
(13)
Cys-X 2 -X 3 -X 4 -X 5 -X 6 -X 7 -X 8 -X 9 -X 10 -X 11 -Cys,
(SEQ ID NO:12)
wherein
X 2 is Arg, Asn, Gln, Glu, His, Leu, Phe, Pro, Trp, Tyr, or Val (preferably Trp, Tyr, or Val);
X 3 is Arg, Asp, Gln, Gly, Ile, Lys, Phe, Thr, Trp or Tyr (preferably Asp);
X 4 is Ala, Arg, Asp, Glu, Gly, Leu, Ser, or Tyr (preferably Asp);
X 5 is Asp, Gln, Glu, Leu, Met, Phe, Pro, Ser, or Tyr (preferably Leu);
X 6 is Asp, Leu, Pro, Thr, or Val (preferably Leu or Thr);
X 7 is Arg, Gln, His, Ile, Leu, Lys, Met, Phe, Thr, Trp or Tyr (preferably Lys or Thr);
X 8 is Ala, Arg, Asn, Gln, Glu, His, Leu, Lys, Met, or Thr (preferably Arg or Leu);
X 9 is Ala, Asn, Gln, Gly, Leu, Lys, Phe, Pro, Thr, Trp, or Tyr (preferably Thr or Trp);
X 10 is Ala, Arg, Gln, His, Lys, Met, Phe, Pro, Thr, Trp, or Tyr (preferably Met or Phe);
X 11 is Arg, Gln, Glu, Gly, His, Leu, Met, Phe, Pro, Ser, Thr, Tyr, or Val (preferably Val);
(14)
Ala-X 2 -X 3 -X 4 -Asp-X 6 -Leu-Thr-X 9 -Leu-X 11 -X 12 -X 13 -X 14 ,
(SEQ ID NO:447)
wherein
X 2 is Asn, Ser, Tyr, Asp, Phe, Ile, Gln, His, Pro, Lys, Leu, Met, Thr, Val, Glu, Ala, Gly, Cys, or Trp (i.e., any amino acid except Arg; preferably Asn);
X 3 is Trp, Glu, Lys, Cys, Leu, Ala, Arg, Gly, or Ser (preferably Trp);
X 4 is Tyr, Phe, Glu, Cys, Asn (preferably Tyr);
X 6 is Pro, Ser, Thr, Phe, Leu, Tyr, Cys, or Ala (preferably Pro or Ser);
X 9 is Lys, Asn, Gln, Gly, or Arg (preferably Lys);
X 11 is Trp, Ser, Thr, Arg, Cys, Tyr, or Lys (preferably Trp);
X 12 is Leu, Phe, Val, Ile, or His (preferably Leu);
X 13 is Pro, Leu, His, Ser, Arg, Asn, Gln, Thr, Val, Ala, Cys, Ile, Phe, or Tyr (i.e., not Asp, Glu, Gly, Lys, Met, or Trp; preferably Pro); and
X 14 is Asp, Glu, Asn, Val, His, Gln, Arg, Gly, Ser, Tyr, Ala, Cys, Lys, Ile, Thr or Leu (i.e., not Phe, Met, Pro, or Trp; preferably Asp); and,
(15)
X 1 -X 2 -Asp-X 4 -Leu-Thr-X 7 -Leu-X 9 -X 10 ,
(SEQ ID NO:448)
wherein
X 1 is Trp, Glu, Lys, Cys, Leu, Ala, Arg, Gly, or Ser (preferably Trp);
X 2 is Tyr, Phe, Glu, Cys, Asn (preferably Tyr);
X 4 is Pro, Ser, Thr, Phe, Leu, Tyr, Cys, or Ala preferably Pro or Ser);
X 7 is Lys, Asn, Gln, Gly, or Arg (preferably Lys);
X 9 is Trp, Ser, Thr, Arg, Cys, Tyr, or Lys (preferably Trp); and
X 10 is Leu, Phe, Val, Ile, or His (preferably Leu).
70 . The method according to claim 69 , wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 20-168 and 186-435, as depicted in Tables 1-8 and 13.
71 . The method according to claim 69 , wherein the BLyS binding polypeptide comprises an amino acid sequence selected from the group consisting of: Ala-Gly-Lys-Glu-Pro-Cys-Tyr-Phe-Tyr-Trp-Glu-Cys-Ala-Val-Ser-Gly (SEQ ID NO: 450); Ala-Gly-Val-Pro-Phe-Cys-Asp-Leu-Leu-Thr-Lys-His-Cys-Phe-Glu-Ala-Gly (SEQ ID NO: 451); Gly-Ser-Ser-Arg-Leu-Cys-His-Met-Asp-Glu-Leu-Thr-His-Val-Cys-Val-His-Phe-Ala-Pro (SEQ ID NO: 452); Gly-Asp-Gly-Gly-Asn-Cys-Tyr-Thr-Asp-Ser-Leu-Thr-Lys-Leu-His-Phe-Cys-Met-Gly-Asp-Glu (SEQ ID NO: 453); Gly-Tyr-Asp-Val-Leu-Thr-Lys-Leu-Tyr-Phe-Val-Pro-Gly-Gly (SEQ ID NO: 454); Trp-Thr-Asp-Ser-Leu-Thr-Gly-Leu-Trp-Phe-Pro-Asp-Gly-Gly (SEQ ID NO: 455); Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO:186); Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO: 456); Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu (SEQ ID NO: 457); Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Val (SEQ ID NO:189); Ala-Asn-Trp-Phe-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO: 309); Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Ser-Leu-Pro-Asp (SEQ ID NO: 458); Ala-Asn-Trp-Tyr-Asp-Pro-Leu-Thr-Lys-Leu-Trp-Phe-Pro-Asp (SEQ ID NO: 353); Ala-Asn-Trp-Tyr-Asp-Ser-Leu-Thr-Lys-Leu-Trp-Leu-Pro-Asp (SEQ ID NO: 327).Join the waitlist — get patent alerts
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