Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Reexamination Certificate
2000-11-28
2003-09-16
Romeo, David S. (Department: 1647)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
C514S003100, C514S004300, C514S365000, C530S300000, C530S303000, C530S350000, C930S120000, C546S269700
Reexamination Certificate
active
06620789
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of Invention
This invention relates to molecules useful as agonists of the insulin-like growth factors (IGFs). More particularly, these molecules inhibit the interaction of an IGF with one or more of its IGF binding proteins. Such molecules can be used, for example, in any methods where the IGFs are used, for example, in treating hyperglycemic, obesity-related, neurological, cardiac, renal, immunologic, and anabolic disorders.
2. Description of Background and Related Art
There is a large body of literature on the actions and activities of IGFs (IGF-I, IGF-II, and IGF variants). Human IGF-I is a 7649-dalton polypeptide with a pI of 8.4 (Rinderknecht and Humbel,
Proc. Natl. Acad. Sci. USA,
73: 2365 (1976); Rinderknecht and Humbel,
J. Biol. Chem.,
253: 2769 (1978)) belonging to a family of somatomedins with insulin-like and mitogenic biological activities that modulate the action of growth hormone (GH). Van Wyk et al.,
Recent Prog. Horm. Res.,
30: 259 (1974); Binoux,
Ann. Endocrinol.,
41: 157 (1980); Clemmons and Van Wyk,
Handbook Exp. Pharmacol.,
57: 161 (1981); Baxter,
Adv. Clin. Chem.,
25: 49 (1986); U.S. Pat. No. 4,988,675; WO 91/03253; WO 93/23071.
Like GH, IGF-I is a potent anabolic protein. See Tanner et al.,
Acta Endocrinol.,
84: 681-696 (1977); Uthne et al.,
J. Clin. Endocrinol. Metab.,
39: 548-554 (1974). See also Ross et al.,
Intensive Care Med.,
19 Suppl. 2: S54-57 (1993), which is a review of the role of insulin, GH, and IGF-I as anabolic agents in the critically ill. IGF-I has hypoglycemic effects similar to those of insulin, but also promotes positive nitrogen balance. Underwood et al.,
Hormone Res.,
24: 166 (1986); Guler et al.,
N. Engl. J. Med.,
317: 137 (1987). Due to this range of activities, IGF-I is being tested in humans for such widely disparate uses as wound healing, treatment of diabetes, reversal of whole body catabolic states, treatment of heart conditions such as congestive heart failure, and treatment of neurological disorders. Guler et al.,
Proc. Natl. Acad. Sci. USA,
85: 4889-4893 (1988); Duerr et al.,
J. Clin. Invest.,
95: 619-627 (1995); and
Science,
264: 772-774 (1994).
U.S. Pat. Nos. 5,273,961; 5,466,670; 5,126,324; 5,187,151; 5,202,119; 5,374,620; 5,106,832; 4,988,675; 5,106,832; 5,068,224; 5,093,317; 5,569,648; and 4,876,242; WO 92/11865; WO 96/01124; WO 91/03253; WO 93/25219; WO 93/08826; and WO 94/16722 disclose various methods of treating mammals, especially human patients, using IGF-I. In addition, clinical uses of IGF-I are described, for example, in Bondy,
Ann Intern. Med.,
120: 593-601 (1994).
As one specific use, IGF-I has been found to exert a variety of actions in the kidney. Hammerman and Miller,
Am. J. Physiol.,
265: F1-F14 (1993). It has been recognized for decades that the increase in kidney size observed in patients with acromegaly is accompanied by a significant enhancement of glomerular filtration rate. O'Shea and Layish,
J. Am. Soc. Nephrol.,
3: 157-161 (1992). U.S. Pat. No. 5,273,961 discloses a method for prophylactic treatment of mammals at risk for acute renal failure. In humans IGF-I has been shown to preserve renal function post-operatively. Franklin et al.,
Am. J. Physiol.,
272: F257-F259 (1997). Infusion of the peptide in humans with normal renal function increases glomerular filtration rate and renal plasma flow. Guler et al.,
Acta Endocrinol.,
121: 101-106 (1989); Guler et al.,
Proc. Natl. Acad. Sci. USA,
86: 2868-2872 (1989); Hirschberg et al.,
Kidney Int.,
43: 387-397 (1993); U.S. Pat. No. 5,106,832. Further, humans with moderately reduced renal function respond to short-term (four days) IGF-I administration by increasing their rates of glomerular filtration and renal plasma flow. Hence, IGF-I is a potential therapeutic agent in the setting of chronic renal failure. O'Shea et al.,
Am. J. Physiol.,
264: F917-F922 (1993). Despite the fact that IGF-I can enhance renal function for those experiencing end-stage chronic renal failure, the enhancements of the glomerular filtration rate and renal plasma flow induced by IGF-I short-term do not persist during long-term administration and incidence of side-effects is high. Miller et al., Kidney International, 46: 201-207 (1994).
For complete reviews of the effect of IGF-I on the kidney, see, e.g., Hammerman and Miller,
Am. J. Physiol.,
265: F1-F14 (1993) and Hammerman and Miller,
J. Am. Soc. Nephrol.,
5: 1-11 (1994).
As to anabolic indications for IGF-I, in HIV-infected patients treated consecutively with IGF-I, the IGF-I promoted anabolism, but tachyphylaxis developed rapidly in the patients. Lieberman et al.,
U.S. Endocrine Meeting,
June 1993 (Abst. 1664); Lieberman et al.,
J. Clin. Endo. Metab.,
78: 404-410 (1994). In patients with severe head injuries, a condition associated with profound hypercatabolism and nitrogen loss, infusion of IGF-I produced only a transient positive nitrogen balance. In the first week the patients experienced a positive nitrogen balance, but during the second week, a negative nitrogen balance developed. Chen et al.,
U.S. Endocrine Meeting,
June 1993 (Abst. 1596).
IGF-I has hypoglycemic effects in humans similar to those of insulin when administered by intravenous bolus injection. Underwood et al., Hormone Research, 24: 166 (1986). IGF-I is known to exert glucose-lowering effects in both normal (Guler et al.,
N. Engl. J. Med.,
supra) and diabetic individuals (Schoenle et al.,
Diabetologia,
34: 675-679 (1991); Zenobi et al.,
J. Clin. Invest.,
90: 2234-2241 (1992); Sherwin et al.,
Hormone Research,
41 (Suppl. 2): 97-101 (1994); Takano et al.,
Endocrinol. Japan,
37: 309-317 (1990); Guler et al.,
Acta Paediatr. Scand.
(Suppl.), 367: 52-54 (1990)), with a time course described as resembling regular insulin. See also Kerr et al., “Effect of Insulin-like Growth Factor 1 on the responses to and recognition of hypoglycemia,” American Diabetes Association (ADA), 52nd Annual Meeting, San Antonio, Tex., Jun. 20-23, 1992, which reported an increased hypoglycemia awareness following recombinant human IGF-I (rhIGF-I) administration. In addition, single administration of rhIGF-I reduces overnight GH levels and insulin requirements in adolescents with IDDM. Cheetham et al.,
Clin. Endocrinol.,
40: 515-555 (1994); Cheetham et al.,
Diabetologia,
36: 678-681 (1993)
The administration of rhIGF-I to Type II diabetics, as reported by Schalch et al.,
J. Clin. Metab.,
77: 1563-1568 (1993), demonstrated a fall in both serum insulin as well as a paralleled decrease in C peptide levels. This indicated a reduction in pancreatic insulin secretion after five days of IGF-I treatment. This effect has been independently confirmed by Froesch et al.,
Horm. Res.,
42: 66-71 (1994). In vivo studies in normal rats also illustrate that IGF-I infusion inhibits pancreatic insulin release. Fursinn et al.,
Endocrinology,
135: 2144-2149 (1994). In addition, in pancreas perfusion preparations, IGF-I also suppressed insulin secretion. Leahy et al.,
Endocrinology,
126: 1593-1598 (1990). Despite these clear in vivo inhibitory effects of IGF-I on insulin secretion in humans and animals, in vitro studies have not yielded such uniform results.
RhIGF-I has the ability to improve insulin sensitivity. For example, rhIGF-I (70 &mgr;g/kg bid) improved insulin sensitivity in non-diabetic, insulin-resistant patients with myotonic dystrophy. Vlachopapadopoulou et al.,
J. Clin. Endo. Metab.,
12: 3715-3723 (1995). Saad et al.,
Diabetologia,
37: Abstract 40 (1994) reported dose-dependent improvements in insulin sensitivity in adults with obesity and impaired glucose tolerance following 15 days of rhIGF-I treatment (25 &mgr;g and 100 &mgr;g/kg bid). RhIGF-I also improved insulin sensitivity and glycemic control in some patients with severe type A insulin resistance (Schoenle et al.,
Diabetologia,
34: 675-679 (1991); Morrow et al.,
Diabetes,
42 (Suppl.): 269 (1993) (abstract); Kuzuya et al.,
Diabetes,
42: 696-705 (1993)) and in other patients with non-insulin dependent diabetes
Clark Ross G.
Lowman Henry B.
Robinson Iain C.A.F.
Genentech Inc.
Hasak, Esq. Janet E.
Heller Ehrman White & McAuliffe LLP
Romeo David S.
LandOfFree
Insulin-like growth factor agonist molecules does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Insulin-like growth factor agonist molecules, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Insulin-like growth factor agonist molecules will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3009488