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Acid-labile subunit (als) of insulin-like growth factor binding protein complexRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureAcid-labile subunit (als) of insulin-like growth factor binding protein complex description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070072799, Acid-labile subunit (als) of insulin-like growth factor binding protein complex. Brief Patent Description - Full Patent Description - Patent Application Claims
FIELD OF INVENTION [0001] This invention relates to a previously unknown and uncharacterised polypeptide, hereinafter referred to as the acid-labile sub-unit (ALS) of insulin like growth factor (IGF) binding protein complex. [0002] Peptides of the insulin-like growth factor (IGF) family resemble insulin both in their structure and in many of their actions. The IGF family consists of two members designated IGF-I and IGF-II (IGFs). The IGFs exhibit a broad spectrum of biological activity, including anabolic insulin-like actions (e.g. stimulation of amino acid transport and glycogen synthesis), mitogenic activity and the stimulation of cell differentiation. [0003] Human IGF-I and IGF-II have been extensively characterized, and have been found to have molecular weight of approximately 7.6 Kd (IGF-I) and 7.47 Kd (IGF-II). [0004] Unlike most peptide hormones, IGFs are found in the circulation (in-vivo) and in cell culture medium in association with one or more binding proteins. The nature of the binding protein or binding proteins associated with the IGFs has been the subject of debate. Wilkins, J. R. and D'Ercole, A. J. (1985, J. Clin. Invest. 75, 1350-1358) have proposed that the in-vivo form of IGF is a complex comprising IGF in association with six identical sub-units having a molecular weight of 24 Kd to 28 Kd. In a second proposal, the in-vivo form of IGF is said to be associated with an acid-stable binding protein and an acid-labile protein(s) to generate a complex of approximately 150 Kd (Furlanetto, R. W. (1980) J. Clin. Endocrinol. Metab. 51, 12-19). [0005] We have previously identified an acid-stable serum protein which has a single IGF-binding site per molecule, is immunologically related to the 150 Kd in-vivo form of IGF and which has an apparent molecular weight of approximately 53 Kd (Baxter, R. C., and Martin, J. L. (1986) J. Clin. Invest. 78, 1504-1512; and Martin, J. L. and Baxter, R. C. (1986) J. Biol. Chem. 261, 8754-8760). This 53 Kd IGF binding protein (BP53) appears to correspond to the acid stable binding protein proposed by Furlanetto. The 53 Kd protein is the highest molecular weight member of a family of acid-stable IGF binding proteins. Other members of this family have approximate molecular weights of 20, 34, 36, 30 and 47 Kd, and collectively fall within the definition "acid-stable IGF binding protein". [0006] We have now surprisingly identified an acid-labile protein, which when incubated with the 53 Kd acid stable protein occupied by IGF converts it to a high molecular weight complex, corresponding to the in-vivo form of IGF. SUMMARY OF THE INVENTION [0007] According to one aspect of the invention there is provided the acid-labile sub-unit (ALS) of insulin like growth factor binding protein complex in biologically pure form, which preferably has the following partial N-terminal amino acid sequence: TABLE-US-00002 GlyAspProGlyThrProGlyGluAlaGluGlyProAlaCysProAla AlaCysAla wherein the first amino acid may be Gly or Ala. [0008] In another aspect of the invention there is provided a composition of matter consisting essentially of the acid-labile sub-unit (ALS) of the insulin like growth factor binding complex. [0009] In another aspect of the invention there is provided a composition, reconstituted from three polypeptide components, namely, IGF, BP-53 and ALS. The composition may be formulated to be in association with one or more pharmaceutically acceptable carriers or excipients. [0010] In yet another aspect of the invention there is provided a process for the preparation of ALS, which comprises the steps of: [0011] (a) applying a source of ALS to a support matrix having attached thereto IGF bound to or associated with the acid-stable IGF binding protein, whereby the ALS in the applied material binds to the acid stable binding protein and non-bound material is separated from the support matrix; and [0012] (b) selectively eluting and recovering the ALS protein from the IGF protein complex. [0013] Preferably, ALS is prepared by a process comprising the steps of: [0014] (a) binding IGF to a support matrix; [0015] (b) adding the acid-stable IGF binding protein to the support matrix such that it binds to or is associated with the IGF; [0016] (c) applying a source of ALS to the support matrix whereby the ALS in the applied material binds to the acid stable protein and non-bound material is separated from the support matrix; [0017] (d) selectively eluting the ALS protein from the IGF protein complex; and [0018] (e) optionally further fractionating the recovered ALS by HPLC or FPLC. [0019] According to a further aspect of the invention there is provided a method for detecting the levels of ALS in body fluids, which comprises fractionating the body fluids on a size fractionation matrix to separate free ALS from the other components of the insulin growth factor binding complex, and thereafter quantitating the levels of ALS in the fractionated sample. [0020] In still another aspect of the invention there is provided a recombinant nucleic acid sequence encoding the acid-labile sub-unit (ALS) of insulin like growth factor. The recombinant nucleic acid sequence preferably encodes a polypeptide having the following partial N-terminal amino acid sequence: TABLE-US-00003 GlyAspProGlyThrProGlyGluAlaGluGlyProAlaCysProAla AlaCysAla. wherein the first amino acid is Gly or Ala. Continue reading about Acid-labile subunit (als) of insulin-like growth factor binding protein complex... Full patent description for Acid-labile subunit (als) of insulin-like growth factor binding protein complex Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Acid-labile subunit (als) of insulin-like growth factor binding protein complex patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. 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