Patent US4746508A successfully refreshed from Google Patents.
US4746508A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Drug administration
Assignee: The Brigham and Women's Hospital Inc
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Filing: 1984-05-25
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Granted: 1988-05-24
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Expires: 2004-05-25
Abstract
Abstract Compositions and methods useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition are provided. The compositions used comprise, in admixture, a biologically-effective amount of a drug specific for the disorder or condition and a biocompatible, water-soluble, amphiphilic steroid, other than a natural bile salt, which is capable of increasing drug permeability of the human or animal body surface across which the drug is to be administered, in an amount effective to increase the permeability of the surface to the drug.
Inventors
- 👤 Martin C. Carey
- 👤 Alan C. Moses
- 👤 Jeffrey S. Flier
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 06:37
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0048; A61K31/00; A61K31/13; A61K31/135; A61K31/137; A61K31/56; A61K31/575; A61K38/00; A61K38/16; A61K38/17; A61K38/22; A61K38/24; A61K38/26; A61K38/28; A61K45/00; A61K45/06; A61K47/00; A61K47/06; A61K47/28; A61K9/0014; A61K9/0043
Claims Analysis
Total Claims: 84
Claim 1
Independent Claim
189 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture; as an active ingredient, a biologically-effective amount of a peptide specific for the particular disorder or condition; and (b) as an adjuvant, a biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR3## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two to three polar functions, exclusive of the function represented by D; said adjuvant being capable of increasing peptide permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 2
Dependent Claim
189 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture; as an active ingredient, a biologically-effective amount of a peptide specific for the particular disorder or condition; and (b) as an adjuvant, a biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR3## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two to three polar functions, exclusive of the function represented by D; said adjuvant being capable of increasing peptide permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 3
Dependent Claim
140 words
The composition of claim 1 wherein said fusidic acid derivative has the formula: ##STR4## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water soluble within a range of about pH 2 to about pH 12; E represents β OAc, α OH, a lower alkyl group in β position, or a lower heteroalkyl group in β position; G represents α OAc, OH, a lower alkyl group, or a lower heteroalkyl group; W represents α OAc or H; Q represents H or OH, provided that, when W is α OAc and Q is OH, Q is β-equatorial; V represents H or α OH; and X represents H or α OH, said steroid containing from two to three OH groups.
Claim 4
Dependent Claim
43 words
The composition of claim 1 wherein the fusidic acid derivative is in unconjugated form, with D being selected from the group consisting of O - Na + , O - K + , O - Rb + and O - Cs + .
Claim 5
Dependent Claim
20 words
The composition of claim 1 wherein D is a covalently linked organic group which contains at least one carbon atom.
Claim 6
Dependent Claim
33 words
The composition of claim 4 wherein the covalently linked organic group is an amino acid containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 7
Dependent Claim
21 words
The composition of claim 5 wherein the amino acid is selected from the group consisting of glycine, taurine, homoglycine and homotaurine.
Claim 8
Dependent Claim
19 words
The composition of claim 5 wherein the amino acid is selected from the group consisting of sulfobetaine and phosphobetaine.
Claim 9
Dependent Claim
40 words
The composition of claim 4 wherein the covalently linked organic group is a peptide of two to three amino acids, said peptide containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 10
Dependent Claim
18 words
The composition of claim 8 wherein the peptide is selected from the group consisting of diglycine and glutathione.
Claim 11
Dependent Claim
19 words
The composition of claim 8 wherein the peptide is selected from the group consisting of sarcosylcysteine, hydroxyprolinetaurine, and sarcosyltaurine.
Claim 12
Dependent Claim
42 words
The composition of claim 4 wherein the covalently linked organic group is a heteroalkyl group of about three or fewer carbon atoms, said group containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 13
Dependent Claim
43 words
The composition of claim 4 wherein the covalently linked organic group is a uronic acid of about six or fewer carbon atoms, said uronic acid containing an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 14
Dependent Claim
45 words
The composition of claim 4 wherein the covalently linked organic group is a polyether containing between about six and about fourteen carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 15
Dependent Claim
24 words
The composition of claim 4 wherein the covalently linked organic group is a polyether containing between about sixteen and about twenty-four carbon atoms, inclusive.
Claim 16
Dependent Claim
45 words
The composition of claim 4 wherein the covalently linked organic group is a polyether containing between about sixteen and about twenty-four carbon atoms, inclusive, said polyether terminating in an ionic function which is dissociated within the range of about pH 2 to about pH 12.
Claim 17
Dependent Claim
28 words
The composition of claim 4 wherein the covalently linked organic group is bonded to C 21 of the fusidic acid derivative by an amide or an ester linkage.
Claim 18
Dependent Claim
31 words
The composition of claim 4 wherein the covalently linked organic group contains an ionic function, said ionic function being SO 3 - , SO 4 - , or COO - .
Claim 19
Dependent Claim
231 words
The composition of claim 2 wherein the fusidic acid derivative is further characterized in that (a) its unconjugated derivative is retained on a column for a length of time sufficient to produce a k' factor value of at least about 4, said k' factor value being obtained by subjecting a monomeric solution of 1 mg/ml of such unconjugated derivative to high-performance (3,000 psi) liquid column chromatography using a 250×4.6 mm column having octadecylsilane-coated 5 μm silica particles as the stationary phase and a mobile phase, delivered at 1.0 ml/min., consisting of 75% methanol in water, v/v, buffered with 0.005 M KHHD 2PO 4 /H 3 PO 4 to give an apparent pH value, as measured using a glass electrode, of pH 5.0, said k' factor value being defined by ##EQU2## where t 0 is the retention time in said column of the solvent front and t r is the retention time in said column of said unconjugated derivative as measured by obtaining the elution profile of said fusidic acid derivative by absorbance at 210 nm; (b) the critical micellar temperature of an aqueous 1% solution, w/v, of the steroid is below about 37° C. within the range of about pH 2 to about pH 12; and (c) the critical micellar concentration of the steroid is less than about 8 mMolar in 0.15M NaCl at 37° C., as measured by surface tension.
Claim 20
Dependent Claim
31 words
The composition of claim 18 wherein the critical micellar temperature of the fusidic acid derivative is below about 20° C. and the critical micellar concentration is less than about 4 mMolar.
Claim 21
Dependent Claim
25 words
The composition of claim 1 wherein the adjuvant is an ionized or partially ionized, water-soluble alkali salt of a fusidic acid or a derivative thereof.
Claim 22
Dependent Claim
117 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a peptide specific for the disorder or condition; (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 , P 2 , P 3 , P 4 or P 5 or a derivative thereof, said cephalosporin or derivative being capable of increasing peptide permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 23
Dependent Claim
117 words
A composition useful for the prevention or treatment of a human or animal disorder or for the regulation of a human or animal physiological condition comprising, in admixture: (a) as an active ingredient, a biologically-effective amount of a peptide specific for the disorder or condition; (b) as an adjuvant, an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 , P 2 , P 3 , P 4 or P 5 or a derivative thereof, said cephalosporin or derivative being capable of increasing peptide permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 24
Dependent Claim
14 words
The composition of claim 20 wherein the derivative of fusidic acid is 24,25-dihydrofusidic acid.
Claim 25
Dependent Claim
14 words
The composition of claim 20 wherein the derivative of fusidic acid is 17,20-24,25-tetrahydrofusidic acid.
Claim 26
Dependent Claim
14 words
The composition of claim 20 wherein the derivative of fusidic acid is 3-acetoxyl-fusidic acid.
Claim 27
Dependent Claim
22 words
The composition of claim 20, 22, 23 or 24 wherein the fusidic acid or derivative thereof is conjugated at C 21 .
Claim 28
Dependent Claim
16 words
The composition of claim 21 wherein the cephalosporin or derivative is conjugated at C 21 .
Claim 29
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-24,25-dihydrofusidate.
Claim 30
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-16α-OH-17,20-24,25-tetrahydrofusidate.
Claim 31
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-16α-OH-24,25-dihydrofusidate.
Claim 32
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-17,20-24,25-tetrahydrofusidate.
Claim 33
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is glyco-24,25-dihydrofusidate.
Claim 34
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-16-O-methyl-ether-24,25-dihydrofusidate.
Claim 35
Dependent Claim
13 words
The composition of claim 20 wherein the derivative of fusidic acid is tauro-16-O-methyl-ether-17,20-24,25-tetrahydrofusidate.
Claim 36
Dependent Claim
22 words
The composition of claim 1, 20 or 21 wherein said peptide has a molecular weight between about 100 and about 300,000 daltons.
Claim 37
Dependent Claim
20 words
The composition of claim 1, 20 or 21 wherein said peptide is a hormone or a precursor or inhibitor thereof.
Claim 38
Dependent Claim
21 words
The composition of claim 1, 20 or 21 wherein said peptide is an enzyme or a precursor or an inhibitor thereof.
Claim 39
Dependent Claim
11 words
The composition of claim 34 wherein said peptide is a glycoprotein.
Claim 40
Dependent Claim
63 words
The composition of claim 1, 20 or 21 wherein said peptide is selected from the group consisting of proinsulin glucagon, parathyroid hormone, parathyroid hormone antagonist, calcitonin, vasopressin, renin, prolactin, growth hormone, thyroid stimulating hormone, corticotropin, corticotropin-releasing factor, follicle stimulating hormone, luteinizing hormone, chorionic gonadotropin, atrial peptides, interferon, tissue plasminogen activator, gammaglobulin, Factor VIII, growth hormone releasing hormone, luteinizing hormone releasing hormone and somatostatin.
Claim 41
Dependent Claim
10 words
The composition of claim 35 wherein the hormone is glucagon.
Claim 42
Dependent Claim
12 words
The composition of claim 35 wherein the hormone is human chorionic gonadotropin.
Claim 43
Dependent Claim
11 words
The composition of claim 35 wherein the hormone is corticotropin-releasing factor.
Claim 44
Dependent Claim
38 words
A composition useful for regulating blood glucose and free fatty acid levels comprising, in admixture: (a) as an active ingredient, a medically-effective amount of glucagon; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 45
Dependent Claim
38 words
A composition useful for regulating blood glucose and free fatty acid levels comprising, in admixture: (a) as an active ingredient, a medically-effective amount of glucagon; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 46
Dependent Claim
35 words
A composition useful for affecting human pregnancy comprising, in admixture: (a) as an active ingredient, a medically-effective amount of human chorionic gonadotropin; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 47
Dependent Claim
35 words
A composition useful for affecting human pregnancy comprising, in admixture: (a) as an active ingredient, a medically-effective amount of human chorionic gonadotropin; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 48
Dependent Claim
36 words
A composition useful for regulating adrenocorticotropin synthesis and release comprising, in admixture: (a) as an active ingredient, a medically-effective amount of corticotropin-releasing hormone; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 49
Dependent Claim
36 words
A composition useful for regulating adrenocorticotropin synthesis and release comprising, in admixture: (a) as an active ingredient, a medically-effective amount of corticotropin-releasing hormone; and (b) as an adjuvant, an effective amount of a salt of tauro-24,25-dihydrofusidate.
Claim 50
Dependent Claim
15 words
The composition of claim 42, 43, or 44 wherein the salt is a sodium salt.
Claim 51
Dependent Claim
35 words
A pharmaceutical preparation suitable for use as a nasal spray or nose drops comprising a solution or suspension of the composition of claim 1, 20, 21, 42, 43, or 44 in a physiologically acceptable carrier.
Claim 52
Dependent Claim
28 words
The pharmaceutical preparation of claim 46 wherein the physiologically acceptable carrier is a sodium phosphate buffer, a sodium phosphate buffered sodium chloride solution, or a sodium chloride solution.
Claim 53
Dependent Claim
29 words
A pharmaceutical preparation suitable for use as eye drops comprising a solution or suspension of the composition of claim 1, 20, 21 or 42 in a physiologically acceptable carrier.
Claim 54
Dependent Claim
52 words
A pharmaceutical preparation in the form of a nasal spray or nose drops useful for the treatment of diabetes comprising a solution or suspension in a physiologically buffered sodium chloride solution of an admixture of a medically-effective amount of insulin as active ingredient and an effective amount of sodium tauro-24,25-dihydrofusidate as adjuvant.
Claim 55
Dependent Claim
52 words
A pharmaceutical preparation in the form of a nasal spray or nose drops useful for the treatment of diabetes comprising a solution or suspension in a physiologically buffered sodium chloride solution of an admixture of a medically-effective amount of insulin as active ingredient and an effective amount of sodium tauro-24,25-dihydrofusidate as adjuvant.
Claim 56
Dependent Claim
197 words
In a method of administering a peptide which comprises applying to a human or animal mucosal surface for absorption across said body surface a composition comprising, as an active ingredient, a peptide specific for a disorder or condition, the improvement which comprises: applying the peptide to the mucosal surface in admixture with biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR5## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two or three polar functions, exclusive of the function represented by D; which biocompatible, water-soluble fusidic acid derivative acts an adjuvant being capable of increasing peptide permeability of the human or animal muscosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 57
Dependent Claim
197 words
In a method of administering a peptide which comprises applying to a human or animal mucosal surface for absorption across said body surface a composition comprising, as an active ingredient, a peptide specific for a disorder or condition, the improvement which comprises: applying the peptide to the mucosal surface in admixture with biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR5## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two or three polar functions, exclusive of the function represented by D; which biocompatible, water-soluble fusidic acid derivative acts an adjuvant being capable of increasing peptide permeability of the human or animal muscosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 58
Dependent Claim
14 words
The method of claim 50 wherein the mucosal surface is a nasal mucosal surface.
Claim 59
Dependent Claim
13 words
The method of claim 50 wherein the mucosal surface is a conjunctival surface.
Claim 60
Dependent Claim
17 words
The method of claim 50 wherein the mucosal surface is an oropharyngeal, nasopharyngeal or respiratory tract surface.
Claim 61
Dependent Claim
16 words
The method of claim 50 wherein the mucosal surface is a vaginal, cervical or endometrial surface.
Claim 62
Dependent Claim
17 words
The method of claim 50 wherein the mucosal surface is a rectal, colonic, gastric or intestinal surface.
Claim 63
Dependent Claim
16 words
The method of claim 50 wherein the mucosal surface is a urethral or urinary bladder surface.
Claim 64
Dependent Claim
20 words
The method of claim 50 wherein the human or animal body surface is an ear canal or tympanic membrane surface.
Claim 65
Dependent Claim
20 words
The method of claim 50 wherein the composition is applied in the form of a nasal spray or nose drops.
Claim 66
Dependent Claim
16 words
The method of claim 50 wherein the composition is applied in the form of eye drops.
Claim 67
Dependent Claim
16 words
The method of claim 50 wherein the composition is applied in the form of a suppository.
Claim 68
Dependent Claim
20 words
The method of claim 50 wherein the composition is applied in the form of a spray, salve, ointment or cream.
Claim 69
Dependent Claim
11 words
The method of claim 50 wherein the drug is a peptide.
Claim 70
Dependent Claim
17 words
The method of claim 50 wherein the peptide is a hormone or a precursor or inhibitor thereof.
Claim 71
Dependent Claim
50 words
The method of claim 63 wherein the hormone is selected from the group consisting of proinsulin, glucagon, parathyroid hormone, calcitonin, vasopressin, renin, prolactin, growth hormone, thyroid stimulating hormone, corticotropin, corticotropin-releasing factor, follicle stimulating hormone, luteinizing hormone, growth hormone releasing hormone, luteinizing hormone releasing hormone and somatostatin or an antagonist thereof.
Claim 72
Dependent Claim
27 words
The method of claim 50 wherein the peptide is selected from the group consisting of interferon, tissue plasminogen activator, atrial peptides, natriuretic peptide, gammaglobulin and Factor VIII.
Claim 73
Dependent Claim
11 words
The method of claim 50 wherein the peptide is a glycoprotein.
Claim 74
Dependent Claim
11 words
The method of claim 66 wherein the glycoprotein is chorionic gonadotropin.
Claim 75
Dependent Claim
42 words
A method of administering glucagon for the regulation of blood glucose and free fatty acid levels which comprises applying to a nasal mucosal surface for absorption across said surface the composition of claim 66 formulated as a nasal spray or nose drops.
Claim 76
Dependent Claim
33 words
A method of administering human chorionic gonadotropin which comprises applying to a nasal mucosal surface for absorption across said surface the composition of claim 43 formulated as a nasal spray or nose drops.
Claim 77
Dependent Claim
32 words
A method of administering corticotropin-releasing factor which comprises applying to a nasal mucosal surface for absorption across said surface the composition of claim 44 formulated as a nasal spray or nose drops.
Claim 78
Independent Claim
225 words
A method of administering a vaccine to a human being or animal to immunize said human being or animal against a particular disease which comprises applying to a human or animal mucosal surface for absorption across said muscosal surface a composition comprising, in admixture: (a) as a vaccinating agent, a biologically-effective amount of a peptide antigen or fragment thereof, said peptide antigen or fragment thereof, said peptide antigen being capable of eliciting an immune response protective against the particular disease; and (b) as an adjuvant, a biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR6## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two to three polar functions, exclusive of the function represented by D; said adjuvant being capable of increasing peptide antigen permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 79
Independent Claim
225 words
A method of administering a vaccine to a human being or animal to immunize said human being or animal against a particular disease which comprises applying to a human or animal mucosal surface for absorption across said muscosal surface a composition comprising, in admixture: (a) as a vaccinating agent, a biologically-effective amount of a peptide antigen or fragment thereof, said peptide antigen or fragment thereof, said peptide antigen being capable of eliciting an immune response protective against the particular disease; and (b) as an adjuvant, a biocompatible, water-soluble, fusidic acid derivative which has the formula: ##STR6## wherein a dashed line represents a single or a double bond; D represents a group having a molecular weight below about 600 daltons which renders an effective amount of said steroid water-soluble within a range of about pH 2 to about pH 12; E and G each represent OAc, OH, a lower alkyl group or a lower heteroalkyl group; W represents OAc or H; and Q, V and X each represent H or OH, said steroid containing from two to three polar functions, exclusive of the function represented by D; said adjuvant being capable of increasing peptide antigen permeability of a human or animal mucosal surface across which the peptide is to be administered, in an amount effective to increase the permeability of said mucosal surface to said peptide.
Claim 80
Dependent Claim
17 words
The method of claim 50 wherein the composition is applied in a long term release dosage form.
Claim 81
Dependent Claim
19 words
The method of claim 72 wherein the long term release dosage form is a slow, continuous or intermittent form.
Claim 82
Dependent Claim
37 words
The method of claim 72 wherein the long term release dosage form is selected from the group consisting of a polymer form, a microcapsule form, a microsphere form, an osmotic diffusion device or a membrane release device.
Claim 83
Dependent Claim
29 words
The method of claim 50 in which the biocompatible, water-soluble, fusidic acid derivative is an ionized or partially ionized, water-soluble alkali salt of fusidic acid or a derivative thereof.
Claim 84
Dependent Claim
42 words
The method of claim 50 in which the biocompatible, water-soluble, fusidic acid derivative is an ionized or partially ionized, water-soluble alkali salt of cephalosporin P 1 , P 2 , P 3 , P 4 or P 5 or a derivative thereof.
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USPTO Annuity & Maintenance Windows
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| 3.5 Years (Year 4) | 1991-05-24 | 1991-11-23 | 1992-05-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1995-05-24 | 1995-11-23 | 1996-05-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1999-05-24 | 1999-11-23 | 2000-05-24 | $7700.00 | Window Closed / Lapsed |