Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2002-11-04
2004-11-23
Housel, James (Department: 1648)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C530S300000, C530S324000
Reexamination Certificate
active
06821949
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to modified insulinotropic peptides. In particular, this invention relates to modified glucagon like peptides and exendin peptides with long duration of action for the treatment of diabetes and other insulinotropic peptide related diseases, gastrointestinal function and activities associated with glucagon levels.
BACKGROUND OF THE INVENTION
The insulinotropic peptide hormone giucagon-like peptide (GLP-1) has been implicated as a possible therapeutic agent for the management of type 2 non-insulin-dependent diabetes mellitus as well as related metabolic disorders, such as obesity. Other useful insulinotropic peptides include exendin 3 and exendin 4. While useful, GLP-1, exendin 3 and exendin 4 suffer from limited duration of action associated with short plasma half-lifes in vivo, mainly due to rapid serum clearance and proteolytic degradation. The enzyme responsible for the degradation of GLP-1, dipeptidyl peptidase IV, has been identified. Extensive work has been done in attempts to inhibit the peptidase or to modify GLP-1 in such a way that its degradation is slowed down while still maintaining biological activity. Despite these extensive efforts, a long lasting, active GLP-1 has not been produced. As such, the diabetic community has a tremendous need for improved GLP-1, exendin 3 and exendin 4 peptides.
There is thus a need to modify GLP-1, exendin 3, exendin 4 and other insulinotropic peptides to provide longer duration of action in vivo, while maintaining their low toxicity and therapeutic advantages.
SUMMARY OF THE INVENTION
In order to meet those needs, the present invention is directed to modified insulinotropic peptides (ITPs). This invention relates to novel chemically reactive derivatives of insulinotropic peptides that can react with available functionalities on cellular carriers including mobile blood proteins to form covalent linkages. Specifically, the invention relates to novel chemically reactive derivatives of insulinotropic peptides such as glucagon like peptide (GLP) and exendin 3 and exendin 4 that can react with available functionalities on mobile blood proteins to form covalent linkages. The invention also relates to novel chemically reactive derivatives or analogs of insulinotropic peptides that can react with available functionalities on mobile blood proteins to form covalent linkages.
The present invention relates to modified insulinotropic peptides comprising a reactive group which reacts with amino groups, hydroxyl groups or thiol groups on blood compounds to form stable covalent bonds.
The present invention relates to an insulinotropic hormone comprising a modified fragment of GLP-1 and derivatives thereof, especially GLP-1 (7-36) amide. The invention additionally pertains to the therapeutic uses of such compounds, and especially to the use of modified GLP-1 (7-36) amide for the treatment of maturity onset diabetes mellitus (type II diabetes).
The present invention further relates to modified Exendin 3 and Exendin 4 fragments and therapeutic uses of such compounds.
In particular, the present invention is directed to GLP-1 (1-36)-Lys
37
(&egr;-MPA)-NH
2
; GLP-1 (1-36)-Lys
37
(&egr;-AAEA-AEEA-MPA)-NH
2
; GLP-1 (7-36)-Lys
37
(&egr;-MPA)-NH
2
; GLP-1 (7-36)-Lys
37−
(&egr;-AEEA-AEEA-MPA)-NH
2
; D-Ala
8
GLP-1 (7-36)-Lys
37
(&egr;-MPA)-NH
2
; Exendin-4 (1-39)-Lys
40
(&egr;-MPA)-NH
2
: Exendin-4 (1-39)-Lys
40
(&egr;-AEEA-AEEA-MPA)-NH
2
; Exendin-3 (1-39)-Lys
40
(&egr;-MPA)-NH
2
; Exendin-3 (1-39)-Lys
40
(&egr;-AEEA-AEEA-MPA)-NH
2
; Lys
26
(&egr;-MPA)GLP-1 (7-36)-NH
2
; GLP-1 (7-36)-EDA-MPA and Exendin-4 (1-39)-EDA-MPA.
The present invention further relates to compositions comprising the derivatives of the insulinotropic peptides and the use of the compositions for treating diabetes in humans.
The invention further pertains to a method for enhancing the expression of insulin which comprises providing to a mammalian pancreatic Beta-type islet cell an effective amount of the modified insulinotropic peptides disclosed above.
The invention further pertains to a method for treating maturity-onset diabetes mellitus which comprises administration of an effective amount of the insulinotropic peptides discussed above to a patient in need of such treatment.
The invention further pertains to the treatment of other insulinotropic peptide related diseases and conditions with the modified insulinotropic peptides of the invention.
REFERENCES:
patent: 5118666 (1992-06-01), Habener
patent: 5120712 (1992-06-01), Habener
patent: 5493007 (1996-02-01), Burnier et al.
patent: 5545618 (1996-08-01), Buckley et al.
patent: 5574008 (1996-11-01), Johnson et al.
patent: 5612034 (1997-03-01), Pouletty et al.
patent: 5612458 (1997-03-01), Hyldig-Nielsen et al.
patent: 5614487 (1997-03-01), Battersby et al.
patent: 5614492 (1997-03-01), Habener
patent: 5958909 (1999-09-01), Habener
patent: 5981488 (1999-11-01), Hoffmann
patent: 6107489 (2000-08-01), Krantz et al.
patent: 6133235 (2000-10-01), Galloway et al.
patent: 6191102 (2001-02-01), DiMarchi et al.
patent: 6329336 (2001-12-01), Bridon et al.
patent: 6528486 (2003-03-01), Larsen et al.
patent: 2002/0049153 (2002-04-01), Bridon et al.
patent: WO 98/20895 (1998-05-01), None
patent: 0602290 (1994-06-01), None
patent: 0969016 (2000-01-01), None
patent: WO 91/11457 (1991-08-01), None
patent: WO 93/25579 (1993-12-01), None
patent: WO 95/10302 (1995-04-01), None
patent: WO 98/08531 (1998-03-01), None
patent: WO 98/08871 (1998-03-01), None
patent: WO 98/08873 (1998-03-01), None
patent: WO 98/43658 (1998-10-01), None
patent: WO 99/24074 (1999-05-01), None
patent: WO 99/24075 (1999-05-01), None
patent: WO 99/29336 (1999-06-01), None
patent: WO 99/48536 (1999-09-01), None
patent: WO 00/76550 (2000-12-01), None
patent: WO 00/76551 (2000-12-01), None
U.S. patent application Ser. No. 10/288,340, Bridon et al., filed Nov. 4, 2002.
U.S. patent application Ser. No. 10/722,733, Bridon et al., filed Nov. 25, 2003.
U.S. patent application Ser. No. 10/723,099, Bridon et al., filed Nov. 25, 2003.
U.S. patent application Ser. No. 09/876,388, Bridon et al., filed Jun. 2000.
U.S. patent application Ser. No. 09/657,332, Bridon et al., filed Sep. 2000.
* Proc. Natl. Acad. Sci., 1983, 80, 5485-5489.
* Nature, 1983, 302, 716-718.
* Endocrinol., 1984, 115, 2176-2181.
* Marburg et al. (1996) “Introduction of the Maleimide Function onto Resin-Bound Peptides: A simple, High yield Process Useful for Discriminating among several lysines,” Bioconjugate Chemistry, vol. 7, pp/ 612-616.
* Anti-Cancer Drugs, 1997, 8, 677-685.
* Siegel et al. (1999) “Biological Activity of GLP-1 analogues with N-terminal modifications,” Regulatory Peptides, vol. 79, issue 23, pp. 93-102.
Ishikawa, E. et al. (Oct. 7, 1978) “Enzyme-Labelling with Maleimides and Its Application to the Immunoassay of Peptide Hormones”Enzyme Labelled Immunoassay of Hormones and Drug, Walter deGruyter & Co., Berlin, New York: 43-57.
Bridon Dominique P.
Ezrin Alan M.
Holmes Darren L.
L'Archeveque Benoit
Leblanc Anouk
ConjuChem Inc.
Housel James
Lucas Zachariah
Morrison & Foerster / LLP
LandOfFree
Long lasting synthetic glucagon-like peptide (GLP-1) does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Long lasting synthetic glucagon-like peptide (GLP-1), we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Long lasting synthetic glucagon-like peptide (GLP-1) will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3316439