US5726152A
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Vascular endothelial cell growth factor II
Assignee: Merck and Co Inc
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Filing: 1994-08-31
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Granted: 1998-03-10
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Expires: 2014-08-31
Abstract
Abstract Vascular endothelial cell growth factor II is purified from the culture media used to maintain mammalian glioma cells. The protein is a heterodimer, stimulates mitogenesis of mammalian vascular endothelial cells and is useful for the promotion of vascular development and repair. This unique growth factor is also useful in the promotion of tissue repair.
Inventors
- 👤 Marvin L. Bayne
- 👤 Gregory L. Conn
- 👤 Kenneth A. Thomas, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 11:27
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/435; C07K14/52
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
232 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and b) a B subunit, wherein said B subunit is a 135 amino acid mature form of a B subunit, wherein said 135 amino acid mature form has the amino acid sequence shown in FIGS. 6 through 6B from Ala 24 to Leu 158, and allelic variants thereof; with said growth factor being substantially free of other proteins.
Claim 2
Dependent Claim
232 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and b) a B subunit, wherein said B subunit is a 135 amino acid mature form of a B subunit, wherein said 135 amino acid mature form has the amino acid sequence shown in FIGS. 6 through 6B from Ala 24 to Leu 158, and allelic variants thereof; with said growth factor being substantially free of other proteins.
Claim 3
Dependent Claim
24 words
A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor II of claim 1.
Claim 4
Dependent Claim
234 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form, of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form, of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and, b) a B subunit, wherein said B subunit is a 115 amino acid mature form of a B subunit, wherein said 115 amino acid mature form has the amino acid sequence shown in FIGS. 7 through 7A from amino acid Ala 24 to Arg 138, and allelic variants, thereof; with said growth factor being substantially free of other proteins.
Claim 5
Dependent Claim
234 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form, of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form, of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and, b) a B subunit, wherein said B subunit is a 115 amino acid mature form of a B subunit, wherein said 115 amino acid mature form has the amino acid sequence shown in FIGS. 7 through 7A from amino acid Ala 24 to Arg 138, and allelic variants, thereof; with said growth factor being substantially free of other proteins.
Claim 6
Dependent Claim
24 words
A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor II of claim 3.
Claim 7
Dependent Claim
241 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form, of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form, of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and b) a B subunit, wherein a mature form of said B subunit is from 115 amino acids to 135 amino acids in length, wherein said mature form has a contiguous amino acid sequence shown in FIGS. 6 through 6B starting at Ala 24 and ending between Arg 138 and Leu 158, inclusive, and allelic variants, thereof, with said growth factor being substantially free of other proteins.
Claim 8
Dependent Claim
241 words
A mammalian vascular endothelial growth factor II, which comprises: a) an A subunit, wherein said A subunit is selected from the group consisting of a 188 amino acid mature form, of an A subunit, wherein said 188 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the substitution of Asn 140 to Lys 140 and the insertion of the amino acid sequence Lys-Ser-Val-Arg-Gly-Lys-Gly-Lys-Gly-Gln-Lys-Arg-Lys-Arg-Lys-Lys-Ser-Arg-Phe-Lys-Ser-Trp-Ser-Val between Lys 140 and His 141; a 164 amino acid mature form, of an A subunit, wherein said 164 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190; and a 120 amino acid mature form of an A subunit, wherein said 120 amino acid mature form has the amino acid sequence shown in FIGS. 5 through 5C from Ala 27 to Arg 190 with the conversion of Asn 140 to Lys 140 and the deletion of the amino acid sequence from His 141 to Arg 184; and b) a B subunit, wherein a mature form of said B subunit is from 115 amino acids to 135 amino acids in length, wherein said mature form has a contiguous amino acid sequence shown in FIGS. 6 through 6B starting at Ala 24 and ending between Arg 138 and Leu 158, inclusive, and allelic variants, thereof, with said growth factor being substantially free of other proteins.
Claim 9
Dependent Claim
24 words
A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor II of claim 5.
Claim 10
Dependent Claim
96 words
A mammalian vascular endothelial growth factor, which comprises either a heterodimer or homodimer of a first and second B subunit, wherein each of said first and second B subunits is independently selected from the group consisting of a 135 amino acid mature form having the amino acid sequence shown in FIGS. 6 through 6B from Ala 24 to Leu 158, a 115 amino acid mature form having the amino acid sequence shown in FIG. 7, from Ala 24 to Arg 138, and allelic variants thereof; with said heterodimer or homodimer being substantially free of other proteins.
Claim 11
Dependent Claim
96 words
A mammalian vascular endothelial growth factor, which comprises either a heterodimer or homodimer of a first and second B subunit, wherein each of said first and second B subunits is independently selected from the group consisting of a 135 amino acid mature form having the amino acid sequence shown in FIGS. 6 through 6B from Ala 24 to Leu 158, a 115 amino acid mature form having the amino acid sequence shown in FIG. 7, from Ala 24 to Arg 138, and allelic variants thereof; with said heterodimer or homodimer being substantially free of other proteins.
Claim 12
Dependent Claim
23 words
A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor of claim 7.
Claim 13
Dependent Claim
88 words
A mammalian vascular endothelial growth factor, which comprises either a heterodimer or homodimer of a first and second B subunit, wherein each of said first and second B subunits comprises a mature form from 115 amino acids in length to 135 amino acids in length, wherein said mature form has a contiguous amino acid sequence shown in FIGS. 6 through 6B starting at Ala 24 and ending between Arg 138 and Leu 158, inclusive, and allelic variants thereof, with said growth factor being substantially free of other proteins.
Claim 14
Dependent Claim
88 words
A mammalian vascular endothelial growth factor, which comprises either a heterodimer or homodimer of a first and second B subunit, wherein each of said first and second B subunits comprises a mature form from 115 amino acids in length to 135 amino acids in length, wherein said mature form has a contiguous amino acid sequence shown in FIGS. 6 through 6B starting at Ala 24 and ending between Arg 138 and Leu 158, inclusive, and allelic variants thereof, with said growth factor being substantially free of other proteins.
Claim 15
Dependent Claim
23 words
A pharmaceutical composition comprising a pharmaceutical carrier and an effective tissue repairing amount of the purified vascular endothelial growth factor of claim 9.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2001-03-09 | 2001-09-08 | 2002-03-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2005-03-09 | 2005-09-08 | 2006-03-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2009-03-09 | 2009-09-08 | 2010-03-10 | $7700.00 | Window Closed / Lapsed |