Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2000-11-07
2003-12-30
Chan, Christina (Department: 1644)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S324000, C530S350000
Reexamination Certificate
active
06670328
ABSTRACT:
The present invention relates to proteins and peptides derived from a protein called Endothelial Cell Specific Molecule -1 (ESM-1).
It relates moreover to the use of such proteins and peptides in the treatment and diagnosis of diseases linked to leukocyte migration, and in particular to inflammatory diseases.
Positioned at the interface between circulating cells and tissues, the endothelial cells play a critical role in the homing and the local accumulation of leukocytes. Initial tethering and rolling, subsequent arrest and adhesion, and transendothelial migration constitute the current view of leukocyte migration. Leukocyte migration involves signal molecules, including selecting, chemoattractants, and integrins, which are present on endothelial cells. Their display of signals is carefully under the control of cytokines; E-selection, vascular cell adhesion molecule-1, IL-8; and RANTES (Regulated on Activation Normal T Cell Expressed) are expressed on endothelial cells only activated by cytokines, whereas ICAM-1, ICAM-2, AND IL-6, which are expressed constitutively in a low rate, are highly induced on endothelial cells in the presence of cytokines.
Vascular endothelium shows diversity among tissues, and there are fewer known mechanisms that regulate leukocyte migration and localization within specific tissues. E-selectin, GlyCAM-1, CD34, and MadCAM-1 contribute to the tissue-specific homing of circulating T-lymphocytes in skin, lymph nodes, and Peyer patches, respectively. GlyCAM-1, CD34, and MadCAM-1 are mucin-like carriers of selectin ligands. CD34 and MadCAM-1 are type 1 membrane glycoproteins, but GlyCAM-1 is secreted by the high endothelial veinules. In the other tissues, very little is known about the presence of such homing molecules on the endothelial cells. Therefore, identification of tissue- and endothelical cell-restricted molecules may contribute to a better understanding of these tissue specific leukocyte-endothelial cell interactions and to find some new method of therapy of diseases related with the leukocyte migration, in particular inflammatory diseases.
General Definitions of Biologically Relevant Terms
In accordance with the present invention there may be employed conventional molecular biology, microbiology, and recombinant DNA techniques within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Sambrook et al., (1989); Glover, (1985); Gait, (1984); Hames and Higgins, (1985); Freshney, (1986); Perbal, (1984); and F. Ausubel et al., (1989).
Therefore, if appearing herein, the following terms shall have the definitions set out below.
The term “isolated” for the purposes of the present invention designates a biological material (nucleic acid or protein) which has been removed from its original environment (the environment in which it is naturally present).
For example, a polynucleotide present in the natural state in a plant or an animal is not isolated. The same polynucleotide separated from the adjacent nucleic acids in which it is naturally inserted in the genome of the plant or animal is considered as being “isolated”.
Such a polynucleotide may be included in a vector and/or such a polynucleotide may be included in a composition and remains nevertheless in the isolated state because of the fact that the vector or the composition does not constitute its natural environment.
The term “purified” does not require the material to be present in a form exhibiting absolute purity, exclusive of the presence of other compounds. It is rather a relative definition.
A polynucleotide is in the “purified” state after purification of the starting material or of the natural material by at least one order of magnitude, preferably 2 or 3 and preferably 4 or 5 orders of magnitude.
For the purposes of the present description, the expression “nucleotide sequence” may be used to designate either a polynucleotide or a nucleic acid. The expression “nucleotide sequence” covers the genetic material itself and is therefore not restricted to the information relating to its sequence.
The terms “nucleic acid”, “polynucleotide”, “oligonucleotide” or “nucleotide sequence” cover RNA, DNA, gDNA or cDNA sequences or alternatively RNA/DNA hybrid sequences of more than one nucleotide, either in the single-stranded form or in the duplex, double-stranded form.
A “nucleic acid” is a polymeric compound comprised of covalently linked subunits called nucleotides. Nucleic acid includes polyribonucleic acid (RNA) and polydeoxyribonucleic acid (DNA), both of which may be single-stranded or double-stranded. DNA includes cDNA, genomic DNA, synthetic DNA, and semi-synthetic DNA. The sequence of nucleotides that encodes a protein is called the sense sequence or coding sequence.
The term “nucleotide” designates both the natural nucleotides (A, T, G, C) as well as the modified nucleotides that comprise at least one modification such as (1) an analog of a purine, (2) an analog of a pyrimidine, or (3) an analogous sugar, examples of such modified nucleotides being described, for example, in the PCT application No. WO 95/04 064.
“Isolated polypeptide” or “isolated protein” is a polypeptide or protein which is substantially free of those compounds that are normally associated therewith in its natural state (e.g., other proteins or polypeptides, nucleic acids, carbohydrates, lipids). “Isolated” is not meant to exclude artificial or synthetic mixtures with other compounds, or the presence of impurities which do not interfere with biological activity, and which may be present, for example, due to incomplete purification, addition of stabilizers, or compounding into a pharmaceutically acceptable preparation.
Polypeptides of the invention include, but are not limited to, those containing, as a primary amino acid sequence, all or part of the amino acid sequence of a polypeptide of SEQ ID NO2 or SEQ ID NO3 according to the invention including altered sequences in which functionally equivalent amino acid residues are substituted for residues within the sequence resulting in a conservative amino acid substitution. For example, one or more amino acid residues within the sequence can be substituted by another amino acid of a similar polarity, which acts as a functional equivalent, resulting in a silent alteration. Substitutes for an amino acid within the sequence may be selected from other members of the class to which the amino acid belongs. For example, the nonpolar (hydrophobic) amino acids include alanine, leucine, isoleucine, valine, proline, phenylalanine, tryptophan and methionine. Amino acids containing aromatic ring structures are phenylalanine, tryptophan, and tyrosine. The polar neutral amino acids include glycine, serine, threonine, cysteine, tyrosine, asparagine, and glutamine. The positively charged (basic) amino acids include arginine, lysine and histidine. The negatively charged (acidic) amino acids include aspartic acid and glutamic acid. Such alterations are not expected to affect apparent molecular weight as determined by polyacrylamide gel electrophoresis, or isoelectric point.
Particularly Preferred Substitutions Are:
Lys for Arg and vice versa such that a positive charge may be maintained;
Glu for Asp and vice versa such that a negative charge may be maintained;
Ser for Thr such that a free —OH can be maintained; and
Gln for Asn such that a free CONH
2
can be maintained.
A “vector” is a replicon, such as plasmid, virus, phage or cosmid, to which another DNA segment-may be attached so as to bring about the replication of the attached segment. It is a circular or a linear DNA or RNA molecule which is either double-stranded or single-stranded. A “replicon” is any genetic element (e.g., plasmid, chromosome, virus) that functions as an autonomous unit of DNA replication in vivo, i.e., capable of replication under its own control.
Identity Between Two Nucleic Acid or Amino Acid Sequences
Identity refers to sequence identity between two peptides or between two nucleic acid molecules. Identity between sequences can be determined by comparing a position in each of the se
Kervoaze Gwenola
Lassalle Phillippe
Marchandise Genevieve
Mollet Sophie
Tonnel Andre Bernard
Institut Pasteur de Lille
Jacobson & Holman PLLC
VanderVegt F. Pierre
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