Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2001-04-30
2003-10-21
Kunz, Gary (Department: 1646)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S008100, C530S353000, C530S395000
Reexamination Certificate
active
06635616
ABSTRACT:
BACKGROUND OF THE INVENTION
Laminins are large heterotrimeric glycoproteins of the extracellular matrix. Each laminin heterotrimer is composed of an &agr;, a &bgr;, and a &ggr; chain, chosen from a number of possible homologues of each chain. Currently, eleven laminin chains have been identified: five &agr; chains, three &bgr; chains, and three &ggr; chains (Timp1 (1996)
Curr Opin Cell Biol
8: 618-624).
SUMMARY OF THE INVENTION
The invention is based, in part, on the discovery of a novel member of the laminin family, laminin 15. Accordingly, the invention features a purified or isolated preparation, a recombinant preparation, or a composition of laminin 15, which includes laminin chains &agr;5, &bgr;2, and &ggr;3. In a preferred embodiment, the laminin 15 is a trimer of an &agr;5, &bgr;2, and &ggr;3 chain. In a preferred embodiment the laminin 15 is human laminin 15.
In a preferred embodiment the &agr;5 chain has a molecular weight of 380 kD, or 330 kD, the &bgr;2 chain has a molecular weight of 190 kD or 170 kD, the &ggr;3 chain has a molecular weight of 220 kD, 200 kD or 170 kD.
In another preferred embodiment, the &agr;5 chain is reactive with or specifically binds an &agr;5-specific antibody, e.g., the mouse monoclonal antibody 4C7 (Engvall et al. (1986)
J Cell Biol
103:2457-2465), or an antibody of the same laminin chain-specificity, e.g., one which can compete for the 4C7 epitope. In another preferred embodiment, the &bgr;2 chain is reactive with or specifically binds a &bgr;2 specific antibody, e.g., a guinea pig polyclonal GP1 (Sanes et al. (1990)
J Cell Biol
111:1685-1699), mouse monoclonal C4 (Sanes et al. (1983)
Cold Spring Harb Symp Quant Biol
48: 667-678), or an antibody of the same laminin chain-specificity, e.g., one which can compete for the GP1 or C4 epitope. In another preferred embodiment, the &ggr;3 chain is reactive with or specifically binds &ggr;3 specific a antibody, e.g., the rabbit antibody R16 or the rabbit antibody R21 (Koch et al. (1999)
J Cell Biol
145: 605-618), or an antibody of the same laminin chain specificity, e.g., one which competes for the R16 or R21 binding site.
In yet another preferred embodiment, the &agr;5 chain has the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4. In a preferred embodiment, the &agr;5 chain is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% 98%, 99% homologous to the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4. In a preferred embodiment, the &agr;5 chain differs from the amino acid sequence of SEQ ID NO: 2 or SEQ ID NO: 4, by at least one, but less than 5, 10, 15 amino acid residues, e.g., by at least one, but less than 5, 10, 15 non-essential amino acid residues. Preferably, the &agr;5 chain retains the ability to form a heterotrimer with the &bgr;2 chain and the &ggr;3 chain.
In another preferred embodiment, the &bgr;2 chain has the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 8. In a preferred embodiment, the &bgr;2 chain is at least 60%, 65%, 70%m, 75%, 80%, 85%, 90%, 95%, 98%, 99% homologous to the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 8. In a preferred embodiment, the &bgr;2 chain differs from the amino acid sequence of SEQ ID NO: 6 or SEQ ID NO: 8, by at least one, but less than 5, 10, 15 amino acid residues, e.g., by at least one, but less than 5, 10, 15 non-essential amino acid residues. Preferably, the &bgr;2 chain retains the ability to form a heterotrimer with the &agr;5 chain and the &ggr;3 chain.
In another preferred embodiment, the &ggr;3 chain has the amino acid sequence of SEQ ID NO: 10. In a preferred embodiment, the &ggr;3 chain is at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98% 99% homologous to the amino acid sequence of SEQ ID NO: 10. In a preferred embodiment, the &ggr;3 chain differs from the amino acid sequence of SEQ ID NO: 10, by at least one, but less than 5, 10, 15 amino acid residues, e.g., by at least one, but less than 5, 10, 15 non-essential amino acid residues. Preferably, the &ggr;3 chain retains the ability to form a heterotrimer with the &agr;5 chain and the &bgr;2 chain.
In another aspect, the invention features, a purified or isolated preparation, a recombinant preparation, or composition of laminin 15, which includes laminin chains &agr;5, &bgr;2, &ggr;3. In a preferred embodiment, the laminin 15 is a trimer of an &agr;5, &bgr;2, and &ggr;3 chain. In a preferred embodiment, the laminin 15 is human laminin 15.
The laminin chains of any laminin as disclosed herein can be the initial translation product or a degradation product, e.g., a naturally occurring degradation product of a laminin chain.
In another aspect, the invention features an isolated nucleic acid, e.g., DNA, RNA or cDNA encoding laminin 15, i.e., which encodes &agr;5, &bgr;2, or &ggr;3. The isolated nucleic acid can be a combination of nucleic acids each encoding one or more laminin 15 chains or a single nucleic acid, e.g., if in a vector, one or more of the chains can be in one vector or each chain can be in a separate vector. The &agr;5 can be, e.g., any &agr;5 chain described herein. In a preferred embodiment, the nucleic acid encoding the &agr;5 chain has the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In a preferred embodiment, the nucleic acid encoding the &agr;5 chain has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% homology, or has the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 3. In another preferred embodiment, the nucleic acid encoding the &agr;5 chain hybridizes, e.g., hybridizes under stringent conditions, to the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 3. The &bgr;2 chain can be, e.g., any &bgr;2 chain described herein. In a preferred embodiment, the nucleic acid encoding the &bgr;2 chain has the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 7. In a preferred embodiment, the nucleic acid encoding the &bgr;2 chain has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% homology, or has the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 7. In another preferred embodiment, the nucleic acid encoding the 132 chain hybridizes, e.g., hybridizes under stringent conditions, to the nucleotide sequence of SEQ ID NO: 5 or SEQ ID NO: 7. The &ggr;3 chain can be, e.g., any &ggr;3 chain described herein. In a preferred embodiment, the nucleic acid encoding the &ggr;3 chain has the nucleotide sequence of SEQ ID NO: 9. In a preferred embodiment, the nucleic acid encoding the &ggr;3 chain has at least 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 98%, 99% homology, or has the nucleotide sequence of SEQ ID NO: 9. In another preferred embodiment, the nucleic acid encoding the &ggr;3 chain hybridizes, e.g., hybridizes under stringent conditions, to the nucleotide sequence of SEQ ID NO: 9.
In a preferred embodiment, the isolated nucleic acid can be expressed in one or more vectors, e.g., an expression vector or expressed directly in a cell. A vector (or vectors) containing a sequence corresponding to the sequence of the isolated nucleic acid can express the isolated nucleic acid in a suitable cell or a suitable in vitro environment.
In another aspect, the invention features producing laminin 15 from a cell transfected with nucleic acid encoding a laminin 15, e.g., a laminin 15 described herein.
In another aspect, the invention features producing laminin 15 from a cell transfected with nucleic acid which encodes one or more of an &agr;5 chain, a &bgr;2 chain and/or a &ggr;3 chain, e.g., a nucleic acid described herein.
In another aspect, the invention features a recombinant laminin 15 which can be produced, e.g., by expressing the laminin chains of laminin 15 in a suitable cell host and under a condition suitable for the laminin chains to form laminin 15.
In a preferred embodiment, the laminin 15 differs from a naturally occurring laminin 15 by at least 1, but less than 5, 10, or 15 amino acid residues. In another embodiment, one, two, or each laminin chain of a laminin, differs from its naturally occurring counterpart by at least 1, but less than 5, 10, or 15 amino acid residues.
The invention provides a method for treating a disord
Brunken William
Burgeson Robert
Champliaud Marie-France
Hunter Dale
Fish & Richardson P.C.
Kunz Gary
Li Ruixiang
The General Hospital Corporation
LandOfFree
Laminin 15 does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Laminin 15, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Laminin 15 will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3166188