CA2446189A1 - Peptides and related molecules that bind to tall-1 - Google Patents

Peptides and related molecules that bind to tall-1 Download PDF

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Publication number
CA2446189A1
CA2446189A1 CA002446189A CA2446189A CA2446189A1 CA 2446189 A1 CA2446189 A1 CA 2446189A1 CA 002446189 A CA002446189 A CA 002446189A CA 2446189 A CA2446189 A CA 2446189A CA 2446189 A1 CA2446189 A1 CA 2446189A1
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amino acid
residue
matter
composition
seq
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CA2446189C (en
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Hosung Min
Hailing Hsu
Fei Xiong
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Amgen Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/08—Linear peptides containing only normal peptide links having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/10—Peptides having 12 to 20 amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/04—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length on carriers
    • C07K1/047—Simultaneous synthesis of different peptide species; Peptide libraries
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/001—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof by chemical synthesis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4702—Regulators; Modulating activity
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7151—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for tumor necrosis factor [TNF], for lymphotoxin [LT]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/24—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
    • C07K16/241—Tumor Necrosis Factors
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1037—Screening libraries presented on the surface of microorganisms, e.g. phage display, E. coli display
    • C—CHEMISTRY; METALLURGY
    • C40—COMBINATORIAL TECHNOLOGY
    • C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
    • C40B40/00—Libraries per se, e.g. arrays, mixtures
    • C40B40/02—Libraries contained in or displayed by microorganisms, e.g. bacteria or animal cells; Libraries contained in or displayed by vectors, e.g. plasmids; Libraries containing only microorganisms or vectors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/74—Fusion polypeptide containing domain for protein-protein interaction containing a fusion for binding to a cell surface receptor

Abstract

The present invention concerns therapeutic agents that modulate the activity of TALL-1. In accordance with the present invention, modulators of TALL-1 may comprise an amino acid sequence Dz2~Lz4~ wherein z2~ is an amino acid residue and z4~ is threonyl or isoleucyl. Exemplary molecules comprise a sequence of the formulae a1~a2~a3~CDa6~La8~a9~a10~Ca12~a13~a14~ (SEQ.ID.NO:100), b1~b2~b3~Cb5~b6~Db8~Lb10~b11~b12~b13~b14~Cb16~b17~b18~ (SEQ.ID.NO:104) c1~c2~c3~Cc5~Dc7~Lc9~c10~c11~c12~c13~c14~Cc16~c17~c18~ (SEQ.ID.NO:105) d1~d2~d3~Cd5~d6~d7~WDd10~Ld13~d14~d15~Cd16~d17~d18~ (SEQ.ID.NO:106) e1~e2~e3~Ce5~e6~e7~De9~Le11~Ke13~Ce15~e16~e17~e18~ (SEQ.ID.NO:107) f1~f2~f3~Kf5~Df7~Lf9~f10~Qf12~f13~f14~ (SEQ.ID NO:109) wherein the substituents are as defined in the specification. The invention further comprises compositions of matter of the formula (X1~)~a-V1~-(X2~)~b wherein V1~ is a vehicle that is covalently attached to one or more of the above TALL-1 modulating compositions of matter. The vehicle and the TALL-1 modulating composition of matter may be linked through the N- or C-terminus of the TALL-1 modulating portion. The preferred vehicle is an Fc domain, and the preferred Fc domain is an IgG Fc domain.

Claims (62)

1. A TALL-1-binding composition of matter comprising an amino acid sequence Dz2Lz4, wherein z2 is an amino acid residue and z4 is T or I, and wherein the composition of matter does not comprise a fragment of TACI, BCMA, or BAFFR(SEQ ID NOS:195,196, and 197).
2. The composition of matter of Claim 1, wherein z4 is T.
3. A TALL-1-binding composition of matter comprising an amino acid sequence Dz2LI, wherein z2 is an amino acid residue.
4. The composition of matter of Claim 1 comprising an amino acid sequence of the formula a1a2a3CDa6La8a9a10Ca12a13a14 (SEQ. ID. NO:100) wherein:
a1, a2, a3 are each independently absent or amino acid residues;
a6 is an amino acid residue;
a8 is T or I;
a9 is a basic or hydrophobic residue;
a12 is a neutral polar residue; and a13 and a14 are each independently absent or amino acid residues.
5. The composition of matter of Claim 4 wherein a8 is T and a9 is a basic residue.
6. The composition of matter of Claim 4 wherein a9 is K and a12 is F.
7. The composition of matter of Claim 1 comprising an amino acid sequence of the formula b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO:104) wherein:
b1 and b2 are each independently absent or amino acid residues;
b3 is an acidic or amide residue;

b5 is an amino acid residue;
b6 is an aromatic residue;
b8 is an amino acid residue;
b10 is T or I;
b11 is a basic residue;
b12 and b13 are each independently amino acid residues;
b14 is a neutral polar residue; and b16, b17, and b18 are each independently absent or amino acid residues.
8. The composition of matter of Claim 7 wherein:
b3 is D, Q, or E;
b6 is W or Y;
b10 is T;
b11 is K or R; and b14 is V or L.
9. The composition of matter of Claim 1 comprising an amino acid sequence of the formula c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO:105) wherein:
c1, c2, and c3 are each independently absent or amino acid residues;
c5 is an amino acid residue;
c7 is an amino acid residue;
c9 is T or I;
c10 is a basic residue;
c11 and c12 are each independently amino acid residues;
c13 is a neutral polar residue;
c14 is an amino acid residue;
c16 is an amino acid residue;
c17 is a neutral polar residue; and c18 is an amino acid residue or is absent.
10. The composition of matter of Claim 9 wherein:
c9 is T;
c10 is K or R;
c13 is a I, L, or V; and c17 is A or L.
11. The composition of matter of Claim 1 comprising an amino acid sequence of the formula d1d2d3Cd5d6d7WDd10Ld12d13d14Cd15d16d17 (SEQ. ID. NO: 106) wherein:
d1, d2, and d3 are each independently absent or amino acid residues;
d5, d6, and d7 are each independently amino acid residues;
d10 is an amino acid residue;
d13 is T or I;
d14 is an amino acid residue; and d16, d17, and d18 are each independently absent or amino acid residues.
12. The composition of matter of Claim 1 comprising an amino acid sequence of the formula e1e2e3Ce5e6e7De9L e11Ke13Ce15e16e17e18 (SEQ. ID. N0:107) wherein:
e1, e2, and e3 are each independently absent or amino acid residues;
e5, e6, e7, e9, and e13 are each independently amino acid residues;
e11 is T or I; and e15, e16, and e17 are each independently absent or amino acid residues.
13. The composition of matter of Claim 1 comprising an amino acid sequence of the formula f1f2f3Kf5Df7Lf9f10Qf12f13f14 (SEQ ID NO:109) wherein:
f1, f2, and f3 are absent or are amino acid residues;
f5 is W, Y, or F;
f7 is an amino acid residue;
f is T or I;
f10 is K, R, or H;
f12 is C, a neutral polar residue, or a basic residue (W, C, or R
preferred);
f13 is C, a neutral polar residue or is absent; and f14 is any amino acid residue or is absent;
provided that only one of f1, f2, and f3 may be C, and only one of f12, f13, and f14 may be C.
14. The composition of matter of Claim 13, wherein f5 is W.
15. The composition of matter of Claim 13, wherein f7 is L.
16. The composition of matter of Claim 13, wherein f9 is T.
17. The composition of matter of Claim 13, wherein f10 is K.
18. The composition of matter of Claim 13, wherein f12 is C and one of f1, f2, and f3 is C.
19. The composition of matter of Claim 13, wherein f13 is V.
20. The composition of matter of Claim 13 comprising an amino acid sequence of the formula f1f2f3KWDf7Lf9KQf12f13f14 (SEQ ID NO: 125).
21. The composition of matter of Claim 20 comprising an amino acid sequence selected from the group consisting of SEQ ID NOS: 32, 33, 58, 60, 63, 66, 67, 69, 114, 115, 122, 123, 124, 147-150, 152-177, 179, 180, and 187.
22. The composition of matter of Claim 20 comprising an amino acid sequence of the formula LPGCKWDLLIKQWVCDPL (SEQ ID NO: 33).
23. A composition of matter comprising an amino acid sequence of the formula g1g2g3Cg5PFg8Wg10Cg11g12g13 (SEQ. ID. NO:101) wherein:
g1, g2 and g3 are each independently absent or amino acid residues;
g5 is a neutral polar residue;
g8 is a neutral polar residue;
g10 is an acidic residue;
g12 and g13 are each independently amino acid residues; and g14 is absent or is an amino acid residue.
24. The composition of matter of Claim 23 wherein:
g2 is G;
g5 is W;
g8 is P;
g10 is E; and g13 is a basic residue.
25. A composition of matter comprising an amino acid sequence of the formula h1h2h3CWh6h7WGh10Ch12h13h14 (SEQ. ID. NO: 102) wherein:
h1, h2, and h3 are each independently absent or amino acid residues;
h6 is a hydrophobic residue;

h7 is a hydrophobic residue;
h10 is an acidic or polar hydrophobic residue; and h12, h13, and h14 are each independently absent or amino acid residues.
26. The composition of matter of Claim 25 wherein:
h1 is G;
h6 is A;
h7 is a neutral polar residue; and h10 is an acidic residue.
27. A composition of matter comprising an amino acid sequence of the formula i1i2i3Ci5i6i7i8i9i10Ci12i13i14 (SEQ. ID. NO: 103) wherein:
i1 is absent or is an amino acid residue;
i2 is a neutral polar residue;
i3 is an amino acid residue;
i5, i6, i7, and i8 are each independently amino acid residues;
i9 is an acidic residue;
i10 is an amino acid residue;
i12 and i13 are each independently amino acid residues; and i14 is a neutral polar residue.
28. The composition of matter of Claim 27 wherein:
i2 is W; and i14 is W.
29. A TALL-1 binding composition of matter comprising an amino acid sequence of the formula PFPWE (SEQ ID NO: 110).
30. The composition of matter of Claim 1 having the formula (X1)a-V1-(X2)b and multimers thereof, wherein:

V1 is a vehicle;
X1 and X2 are each independently selected from -(L1)c-P1, -(L1)c-P1-(L2)d-P2, -(L1)c-P1-(L2)d-P2-(L3)e-P3, and -(L1)c-P1-(L2)d-P2-(L3)e-P3-(L4)f-P4 one or more of P1, P2, P3, and P4 each independently comprise Dz2Lz4;
L1, L2, L3, and L4 are each independently linkers; and a, b, c, d, e, and f are each independently 0 or 1, provided that at least one of a and b is 1.
31. The composition of matter of Claim 30 of the formula P1-(L1)c-P2-(L2)d'-V1.
32. The composition of matter of Claim 30 of the formula V1-(L1)c-P1-(L2)d-P2.
33. The composition of matter of Claim 30, wherein V1 is an Fc domain.
34. The composition of matter of Claim 30 wherein V1 is an IgG Fc domain.
35. The composition of matter of Claim 30 wherein V1 is an IgG1 Fc domain.
36. The composition of matter of Claim 30 wherein V1 comprises the sequence of SEQ ID NO: 2.
37. The composition of matter of Claim 30 wherein one or more of P1, P2, P3, and P4 each independently comprises a sequence selected from:
a1a2a3CDa6La8a9a10Ca12a13a14 (SEQ. ID. NO:100) b1b2b3Cb5b6Db8Lb10b11b12b13b14Cb16b17b18 (SEQ. ID. NO: 104) c1c2c3Cc5Dc7Lc9c10c11c12c13c14Cc16c17c18 (SEQ. ID. NO: 105) d1d2d3Cd5d6d7WDd10Ld13d14d15Cd16d17d18 (SEQ. ID. NO:106) e1e2e3Ce5e6e7De9Le11Ke13Ce15e16e17e18 (SEQ. ID. NO:107) f1f2f3Kf5Df7Lf9f10Qf12f13f14 (SEQ. ID. NO: 109) g1g2g3Cg5PFg5Wg10Cg11g12g13 (SEQ ID NO: 101), h1h2h3CWh6h7WGh10Ch12h13h14 (SEQ ID NO:102), and i1i2i3Ci5i6i7i8i9i10Ci12i13i14 (SEQ ID NO: 103) wherein:
a1, a2, a3 are each independently absent or amino acid residues;
a6 is an amino acid residue;
a9 is a basic or hydrophobic residue;
a8 is threonyl or isoleucyl;
a12 is a neutral polar residue;
a13 and a14 are each independently absent or amino acid residues;
b1 and b2 are each independently absent or amino acid residues;
b3 is an acidic or amide residue;
b5 is an amino acid residue;
b6 is an aromatic residue;
b8 is an amino acid residue;
b10 is T or I;
b11 is a basic residue;
b12 and b13 are each independently amino acid residues;
b14 is a neutral polar residue;
b16, b17, and b18 are each independently absent or amino acid residues;
c1, c2, and c3 are each independently absent or amino acid residues;
c5 is an amino acid residue;
c7 is an amino acid residue;
c9 is T or I;
c10 is a basic residue;
c11 and c12 are each independently amino acid residues;
c13 is a neutral polar residue;
c14 is an amino acid residue;
c16 is an amino acid residue;

c17 is a neutral polar residue; and c18 is an amino acid residue or is absent;
d1, d2, and d3 are each independently absent or amino acid residues;
d5, d6, and d7 are each independently amino acid residues;
d10 is an amino acid residue;
d12 is T or I;
d13 is an amino acid residue; and d15, d16, and d17 are each independently absent or amino acid residues;
e1, e2, and e3 are each independently absent or amino acid residues;
e5, e6, e7, e9, and e13 are each independently amino acid residues;
e11 is T or I; and e15, e16, and e17 are each independently absent or amino acid residues;
f1, f2, and f3 are absent or are amino acid residues;
f5 is W, Y, or F;
f7 is an amino acid residue;
f9 is T or I;
f10 is K, R, or H;
f12 is C, a neutral polar residue, or a basic residue;
f13 is C, a neutral polar residue or is absent; and f14 is any amino acid residue or is absent;
provided that only one of f1, f2, and f3 may be C, and only one of f12, f13, and f14 may be C;
g1, g2 and g3 are each independently absent or amino acid residues;
g5 is a neutral polar residue;
g8 is a neutral polar residue;
g10 is an acidic residue;
g12 and g13 are each independently amino acid residues; and g14 is absent or is an amino acid residue;
h1, h2, and h3 are each independently absent or amino acid residues;

h6 is a hydrophobic residue;
h7 is a hydrophobic residue;
h10 is an acidic or polar hydrophobic residue; and h12, h13, and h14 are each independently absent or amino acid residues;
i1 is absent or is an amino acid residue;
i2 is a neutral polar residue;
i3 is an amino acid residue;
i5, i6, i7, and i8 are each independently amino acid residues;
i9 is an acidic residue;
i10 is an amino acid residue;
i12 and i13 are each independently amino acid residues; and i14 is a neutral polar residue.
38. The composition of matter of claim 37, wherein:
a9 is a basic residue.
b3 is D, Q, or E;
b6 is W or Y;
b11 is K or R; and b14 is V or L.
c10 is K or R;
c13 is a I, L, or V;
c17 is A or L;
f5 is W;
f7 is L; f7 is K; and f10 is V.
39. The composition of matter of Claim 37, wherein one or more of P1, P2, P3, and P4 each independently comprises f1f2f3KWDf7Lf9KQf12f13f14 (SEQ ID NO: 125).
40. The composition of matter of Claim 39 of the formula P1-(L1)c-P2-(L2)d'-V1.
41. The composition of matter of Claim 39 of the formula V1-(L1)c-P1-(L2)d-P2.
42. The composition of matter of Claim 39 having an amino acid sequence selected from SEQ ID NOS: 122,123, and 124.
43. The composition of matter of Claim 40 wherein L2 is greater than 5 amino acids.
44. The composition of matter of Claim 43 wherein L2 is selected from GSGSATGGSGSTASSGSGSATx1x2 (SEQ ID NO: 193) and GSGSATGGSGSTASSGSGSATx1x2GSGSATGGSGSTASSGSGSATx3x4 (SEQ ID NO:194) wherein x1 and x3 are each independently basic or hydrophobic residues and x2 and x4 are each independently hydrophobic residues.
45. The composition of matter of Claim 41 wherein L2 is selected from GSGSATGGSGSTASSGSGSATH
(SEQ ID NO: 59), GSGSATGGSGSTASSGSGSATGM
(SEQ ID NO:190) GSGSATGGSGSTASSGSGSATGS
(SEQ ID NO: 192), and GSGSATGGSGSTASSGSGSATHMGSGSATGGSGSTASSGSGSATHM
(SEQ ID NO: 192).
46. The composition of matter of Claim 28 comprising a sequence selected from Table 2 (SEQ ID NOS: 29-39, 60-70, and 126-188).
47. The composition of matter of Claim 30 comprising a sequence selected from Table 4 (SEQ ID NOS: 44-55).
48. The composition of matter of Claim 46, wherein V1 is an Fc domain.
49. The composition of matter of Claim 46, wherein V1 is an IgG Fc domain.
50. The composition of matter of Claim 46, wherein V1 is an IgG1 Fc domain.
51. A DNA encoding a composition of matter of Claim 34.
52. An expression vector comprising the DNA of Claim 51.
53. A host cell comprising the expression vector of Claim 52.
54. The cell of Claim 53, wherein the cell is an E, coli cell.
55. A method of treating a B-cell mediated autoimmune disease, which comprises administering a composition of matter of Claim 1.
56. A method of treating a B-cell mediated autoimmune disease, which comprises administering a composition of matter of Claim 13.
57. A method of treating lupus, which comprises administering a composition of matter of Claim 1.
58. A method of treating lupus, which comprises administering a composition of matter of Claim 13.
59. A method of treating a B-cell mediated cancer, which comprises administering a composition of matter of Claim 1.
60. A method of treating a B-cell mediated cancer, which comprises administering a composition of matter of Claim 13.
61. A method of treating B-cell lymphoma, which comprises administering a composition of matter of Claim 1.
62. A method of treating B-cell lymphoma, which comprises administering a composition of matter of Claim 13.
CA2446189A 2001-05-11 2002-05-13 Peptides and related molecules that bind to tall-1 Expired - Fee Related CA2446189C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US29019601P 2001-05-11 2001-05-11
US60/290,196 2001-05-11
PCT/US2002/015273 WO2002092620A2 (en) 2001-05-11 2002-05-13 Peptides and related molecules that bind to tall-1

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CA2446189A1 true CA2446189A1 (en) 2002-11-21
CA2446189C CA2446189C (en) 2011-10-18

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