Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Recombinant dna technique included in method of making a...
Reexamination Certificate
1998-10-19
2001-01-30
Carlson, Karen Cochrane (Department: 1653)
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Recombinant dna technique included in method of making a...
C435S320100, C435S252300, C435S325000, C536S023100, C530S350000
Reexamination Certificate
active
06180364
ABSTRACT:
The present invention concerns a new protein called placentin or EPIL, its analogs, the procedures for their preparation and their applications.
Insulin, IGF1, IGF2 and relaxin belong to a family of peptide hormones having certain common structures and functions, particularly their influence upon cell proliferation, development, differentiation and metabolism.
Insulin is well known as being an endocrine pancreatic hormone regulating energy metabolism. Growth factors of insulin-IGF-1 type are growth promoting peptides involved in endocrine, paracrine and autocrine regulation of cell growth and which are expressed in numerous Tissues. IGF2 has similar properties but is expressed in higher quantities during the prenatal period and is considered as being a fetal growth factor.
Relaxin induces remodeling of connective tissue in the reproductive tract and inhibits uterine contractions. Its functional role in the brain, where extensive expression has been obtained, remains to be elucidated.
Recently, Ley-I-Ls were added to this family which are currently cloned in cDNA form and whose biological activity remains to be determined. This peptide family commonly presents structural characteristics defined by the position of different cysteines essential for the formation of a tertiary structure.
Insulin, which is the prototype for this family, comprises two peptide A and B chains connected by disulfide bridges. It is coded by a mRNA which is translated into preproinsulin. The peptide signal, like the connecting C peptide, are excised by post-translational modification; this also applies to relaxin although the IGFs are matured differently without elimination of the C peptide and remain as a single chain. It has been shown that all the members of this family attach themselves to cell surface receptors. These receptors have been identified by molecular cloning and characterized in detail for insulin and IGF. They belong to the superfamily of tyrosine protein kinase receptors (Tyr-PK receptors) which comprises growth factor receptors and their oncogene analogs such as c-neu/erb-B-2 (EGF receptor), c-met (hepatocyte growth factor receptor), fms (CSF-1 receptor) and trk (NGF receptor).
The transduction route of the intracellular signal for these receptors is characterized by tyrosine-kinase activity which produces autophosphorylation of the tyrosine residues on the receptor followed by a chain of events corresponding to phosphorylations. This includes, in particular, the activation of IRS-1 (particularly for insulin and IGF), P13K, Shc, GBRZ, Sos, Ras, Raf and the kinase mitogenesis activating protein (MAP) especially when the cascade of phosphorylation affects different cell processes such as transcription.
The pleiotropic physiological effects of this cascade of signals are generally the subject of intense research.
REFERENCES:
patent: 273369 (1970-06-01), None
patent: 48-030370 (1974-11-01), None
“Active Preparation Form Human Placental Tissue”, (Database Biosis-Abstract), vol. 5 pp. 120-122 (1969).
“Amino Acid Composition of New Blood Substituted from the Placenta”, Altunyan et al. (Chem. Abstracts), vol. 78, No. 22 (Jun. 4, 1973).
French Preliminary Search Report; Date of completion of search: Feb. 6, 1995.
Bellet Dominique
Chassin Dorine
Koman Ahmet
Burns Doane Swecker & Mathis L.L.P.
Carlson Karen Cochrane
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