Catalytically active recombinant memapsin and methods of use...

Details Catalytically active recombinant memapsin and methods of use... Catalytically active recombinant memapsin and methods of use...

2007-08-03

2010-11-09

Tsang, Cecilia (Department: 1654)

Chemistry: natural resins or derivatives; peptides or proteins;

Proteins, i.e., more than 100 amino acid residues

Reexamination Certificate

active

07829669

ABSTRACT:
Methods for the production of purified, catalytically active, recombinant memapsin 2 have been developed. The substrate and subsite specificity of the catalytically active enzyme have been determined. The substrate and subsite specificity information was used to design substrate analogs of the natural memapsin 2 substrate that can inhibit the function of memapsin 2. The substrate analogs are based on peptide sequences, shown to be related to the natural peptide substrates for memapsin 2. The substrate analogs contain at least one analog of an amide bond which is not capable of being cleaved by memapsin 2. Processes for the synthesis of two substrate analogues including isosteres at the sites of the critical amino acid residues were developed and the substrate analogues, OMR99-1 and OM99-2, were synthesized. OM99-2 is based on an octapeptide Glu-Val-Asn-Leu-Ala-Ala-Glu-Phe (SEQ ID NO:28) with the Leu-Ala peptide bond substituted by a transition-state isostere hydroxyethylene group (FIG.1). The inhibition constant of OM99-2 is 1.6×10−9M against recombinant pro-memapsin 2. Crystallography of memapsin 2 bond to this inhibitor was used to determine the three dimensional structure of the protein, as well as the importance of the various residues in binding. This information can be used by those skilled in the art to design new inhibitors, using commercially available software programs and techniques familiar to those in organic chemistry and enzymology, to design new inhibitors to memapsin 2, useful in diagnostics and for the treatment and/or prevention of Alzheimer's disease.

REFERENCES:
patent: 4235871 (1980-11-01), Papahadjopoulos et al.
patent: 4235877 (1980-11-01), Fullerton
patent: 4391904 (1983-07-01), Litman et al.
patent: 4501728 (1985-02-01), Geho et al.
patent: 4797368 (1989-01-01), Carter et al.
patent: 4837028 (1989-06-01), Allen
patent: 4923967 (1990-05-01), Bobbitt et al.
patent: 4945050 (1990-07-01), Sanford et al.
patent: 4946778 (1990-08-01), Ladner et al.
patent: 5019369 (1991-05-01), Presant et al.
patent: 5036006 (1991-07-01), Sanford et al.
patent: 5132405 (1992-07-01), Huston et al.
patent: 5139941 (1992-08-01), Muzyczka et al.
patent: 5173414 (1992-12-01), Lebkowski et al.
patent: 5187074 (1993-02-01), Treiber et al.
patent: 5192668 (1993-03-01), Treiber et al.
patent: 5200339 (1993-04-01), Abraham
patent: 5204253 (1993-04-01), Sanford et al.
patent: 5219740 (1993-06-01), Miller et al.
patent: 5221607 (1993-06-01), Cordell et al.
patent: 5235043 (1993-08-01), Collins et al.
patent: 5252463 (1993-10-01), Nelson et al.
patent: 5279833 (1994-01-01), Rose
patent: 5286634 (1994-02-01), Stadler et al.
patent: 5308854 (1994-05-01), Hoffman, Jr. et al.
patent: 5413999 (1995-05-01), Vacca et al.
patent: 5476874 (1995-12-01), Hungate et al.
patent: 5502060 (1996-03-01), Thompson et al.
patent: 5545806 (1996-08-01), Lonberg et al.
patent: 5545807 (1996-08-01), Surani et al.
patent: 5569825 (1996-10-01), Lonberg et al.
patent: 5578597 (1996-11-01), Spector et al.
patent: 5580859 (1996-12-01), Felgner et al.
patent: 5589466 (1996-12-01), Felgner et al.
patent: 5591624 (1997-01-01), Barber et al.
patent: 5625126 (1997-04-01), Lonberg et al.
patent: 5633425 (1997-05-01), Lonberg et al.
patent: 5661016 (1997-08-01), Lonberg et al.
patent: 5663169 (1997-09-01), Young et al.
patent: 5679647 (1997-10-01), Carson et al.
patent: 5703055 (1997-12-01), Felgner et al.
patent: 5733768 (1998-03-01), Dixon et al.
patent: 5736524 (1998-04-01), Content et al.
patent: 5739118 (1998-04-01), Carrano et al.
patent: 5744346 (1998-04-01), Chrysler et al.
patent: 5804566 (1998-09-01), Carson et al.
patent: 5846978 (1998-12-01), Coburn et al.
patent: 5922687 (1999-07-01), Mann et al.
patent: 5942400 (1999-08-01), Anderson et al.
patent: 5978740 (1999-11-01), Armistead
patent: 5986054 (1999-11-01), St. George-Hyslop et al.
patent: 6015686 (2000-01-01), Dubensky, Jr. et al.
patent: 6077682 (2000-06-01), Inouye et al.
patent: 6207710 (2001-03-01), Audia et al.
patent: 6245884 (2001-06-01), Hook
patent: 6291223 (2001-09-01), Christie et al.
patent: 6313268 (2001-11-01), Hook
patent: 6319689 (2001-11-01), Powell et al.
patent: 6329163 (2001-12-01), Anderson et al.
patent: 6361975 (2002-03-01), Christie et al.
patent: 6420534 (2002-07-01), Gurney et al.
patent: 6545127 (2003-04-01), Tang et al.
patent: 6699671 (2004-03-01), Gurney et al.
patent: 6790610 (2004-09-01), Gurney et al.
patent: 6844148 (2005-01-01), Gurney et al.
patent: 6852482 (2005-02-01), Chrysler et al.
patent: 7115410 (2006-10-01), Anderson et al.
patent: 7244708 (2007-07-01), Tang et al.
patent: 7678760 (2010-03-01), Tang et al.
patent: 2002/0037315 (2002-03-01), Gurney et al.
patent: 2002/0055459 (2002-05-01), Chopra et al.
patent: 2002/0072050 (2002-06-01), Hook et al.
patent: 2002/0081634 (2002-06-01), Gurney et al.
patent: 2002/0111365 (2002-08-01), Wolfe et al.
patent: 2002/0115600 (2002-08-01), Tang et al.
patent: 2002/0157122 (2002-10-01), Wong et al.
patent: 2002/0159991 (2002-10-01), Cordell et al.
patent: 2002/0164760 (2002-11-01), Lin et al.
patent: 2003/0092629 (2003-05-01), Tang et al.
patent: 2004/0121947 (2004-06-01), Tang et al.
patent: 2004/0220079 (2004-11-01), Tang et al.
patent: 2004/0234976 (2004-11-01), Gurney et al.
patent: 2008/0021196 (2008-01-01), Tang et al.
patent: 2009/0214554 (2009-08-01), Chang et al.
patent: 0 302 469 (1989-02-01), None
patent: 0 855 444 (1998-07-01), None
patent: 1 496 124 (2005-01-01), None
patent: 10 108 681 (1998-04-01), None
patent: 10-327875 (1998-12-01), None
patent: WO-89/03429 (1989-04-01), None
patent: WO 91/02805 (1991-03-01), None
patent: WO-91/02805 (1991-03-01), None
patent: WO-91/06309 (1991-05-01), None
patent: WO-91/12882 (1991-09-01), None
patent: WO-92/01070 (1992-01-01), None
patent: WO-92/03545 (1992-03-01), None
patent: WO-93/03769 (1993-03-01), None
patent: WO-93/24640 (1993-12-01), None
patent: WO-93/24640 (1993-12-01), None
patent: WO-93/24641 (1993-12-01), None
patent: WO-93/24641 (1993-12-01), None
patent: WO-94/26877 (1994-11-01), None
patent: WO-96/40885 (1996-12-01), None
patent: WO-97/27296 (1997-07-01), None
patent: WO-98/04720 (1998-02-01), None
patent: WO-98/13488 (1998-04-01), None
patent: WO-98/15828 (1998-04-01), None
patent: WO-98/21589 (1998-05-01), None
patent: WO-98/26059 (1998-05-01), None
patent: WO-99/51752 (1999-10-01), None
patent: WO-99/64587 (1999-11-01), None
patent: WO-00/17369 (2000-03-01), None
patent: WO-00/23576 (2000-04-01), None
patent: WO-00/47618 (2000-08-01), None
patent: WO-00/58479 (2000-10-01), None
patent: WO-00/77030 (2000-12-01), None
patent: WO-01/00663 (2001-01-01), None
patent: WO-01/00663 (2001-01-01), None
patent: WO-01/00665 (2001-01-01), None
patent: WO-01/00665 (2001-01-01), None
patent: WO-01/23533 (2001-04-01), None
patent: WO-01/49097 (2001-07-01), None
patent: WO-01/49097 (2001-07-01), None
patent: WO-01/49098 (2001-07-01), None
patent: WO-01/49098 (2001-07-01), None
patent: WO-01/50829 (2001-07-01), None
patent: WO-01/50829 (2001-07-01), None
patent: WO-01/00672 (2001-09-01), None
patent: WO-02/25276 (2002-03-01), None
patent: WO-02/47466 (2002-06-01), None
patent: WO-2007/021886 (2007-02-01), None
patent: WO-2007/021886 (2007-02-01), None
Misawa, S. (Sep. 10, 1996). “Purification of Recombinant Proteins fromE. coli,” Chapter 9in Protein Laboratory Notebook, Okada, M. et al. eds., Yodosha: Tokyo, Japan, 2:139-145, Certified Translation.
Aharanov, A. et al. (1974). “Immunogenicity and Antigenic Specificity of a Glutaraldehyde Cross-Linked Transfer RNA-Protein Conjugate,”European Journal of Biochemistry42:73-79.
Åkerström, B. et al. (Oct. 1985). “Protein G: A Powerful Tool for Binding and Detection of Monoclonal and Polyclonal Antibodies,”The Journal of Immunology135(4):2589-2592.
Ali, M. et al. (Nov. 1994). “The Use of DNA Viruses as Vectors for Gene Therapy,”Gene Therapy1(6):367-384.
Asai, D.J. ed. (1993).Methods in Cell Biology: Antibodies in Cell Biology, Academic Press, Inc.: San Diego, CA, 37:vii-xi (Table of Contents Only.).

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