US5374431A
Expired / Lapsed
US
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Synthetic bioadhesive
Assignee: Creative Biomolecules Inc
•
Filing: 1992-12-10
•
Granted: 1994-12-20
•
Expires: 2012-12-10
Abstract
Abstract This invention pertains to a synthetic adhesive composition for use in aqueous environments. The composition comprises polypeptide chains having an alpha -helical structure in aqueous environments and capable of cohesive and adhesive interactions. The polypeptide chains comprise polar and apolar amino acids, the apolar and polar amino acids being arranged to define apolar and polar vertical spiraling stripes on the helix surface. The apolar stripes allow the polypeptide chains to aggregate into superhelical structures and the polar stripes allow interchain crosslinking within and between the superhelical structures.
Inventors
- 👤 Roy H. L. Pang
- 👤 Charles M. Cohen
- 👤 Peter C. Keck
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-31 13:25
CPC Classifications
C; C07; C07K; C07K14/00; C07K14/001; A; A61; A61L; A61L24/00; A61L24/04; A61L24/10; A61L24/106; A61L27/00; A61L27/14; A61L27/22; A61L27/227; A61P; A61P43/00
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
137 words
A synthetic composition for use as an adhesive in aqueous environment comprising: a plurality of polypeptide chains, each polypeptide chain having a helical structure in aqueous environments and one or more copies of the amino acid sequence (Seq. Listing ID No. 2): (Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.1).sub.b wherein b is a number from 1 to 100; each Xaa 1 is independently selected from the group of apolar amino acids consisting of leucine, isoleucine, valine, alanine, glycine, phenylalanine, and methionine; each Xaa 2 and Xaa 3 is an independently selected crosslinkable, surface adherable amino acid adapted to form interchain crosslinks between said helical polypeptide chains such that, when crosslinked, said plurality of polypeptide chains form an insoluble matrix having adhesive properties sufficient to adhere cells in an aqueous environment.
Claim 2
Dependent Claim
137 words
A synthetic composition for use as an adhesive in aqueous environment comprising: a plurality of polypeptide chains, each polypeptide chain having a helical structure in aqueous environments and one or more copies of the amino acid sequence (Seq. Listing ID No. 2): (Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.1).sub.b wherein b is a number from 1 to 100; each Xaa 1 is independently selected from the group of apolar amino acids consisting of leucine, isoleucine, valine, alanine, glycine, phenylalanine, and methionine; each Xaa 2 and Xaa 3 is an independently selected crosslinkable, surface adherable amino acid adapted to form interchain crosslinks between said helical polypeptide chains such that, when crosslinked, said plurality of polypeptide chains form an insoluble matrix having adhesive properties sufficient to adhere cells in an aqueous environment.
Claim 3
Dependent Claim
34 words
The composition of claim 1 wherein the polypeptide chains comprise one or more copies of the amino acid sequence (Seq. Listing ID No. 3): (Ala-Ala-Ala-Lys-Tyr-Lys-Ala-Ala-Ala-Ala-Tyr-Lys-Tyr-Ala).sub.b where b is a number from 1 to 100.
Claim 4
Dependent Claim
135 words
A synthetic matrix having substantial adhesive properties in aqueous environments, said matrix comprising: a plurality of crosslinked polypeptide chains, each polypeptide chain having a helical structure in aqueous environments and one or more copies of the amino acid sequence (Seq. Listing ID No. 2) (Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 Xaa.sub.1 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.1).sub.b wherein b is a number from 1 to 100; each Xaa 1 is independently selected from the group of apolar amino acids consisting of leucine, isoleucine, valine, alanine, glycine, phenylalanine, and methionine, and each Xaa 2 and Xaa 3 is an independently selected crosslinkable, polar, surface adherable amino acid adapted to form interchain crosslinks between said helical polypeptide chains, the crosslinked structures forming an insoluble matrix having adhesive properties sufficient to adhere cells in an aqueous environment.
Claim 5
Dependent Claim
135 words
A synthetic matrix having substantial adhesive properties in aqueous environments, said matrix comprising: a plurality of crosslinked polypeptide chains, each polypeptide chain having a helical structure in aqueous environments and one or more copies of the amino acid sequence (Seq. Listing ID No. 2) (Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.1 -Xaa.sub.1 -Xaa.sub.1 Xaa.sub.1 -Xaa.sub.3 -Xaa.sub.2 -Xaa.sub.3 -Xaa.sub.1).sub.b wherein b is a number from 1 to 100; each Xaa 1 is independently selected from the group of apolar amino acids consisting of leucine, isoleucine, valine, alanine, glycine, phenylalanine, and methionine, and each Xaa 2 and Xaa 3 is an independently selected crosslinkable, polar, surface adherable amino acid adapted to form interchain crosslinks between said helical polypeptide chains, the crosslinked structures forming an insoluble matrix having adhesive properties sufficient to adhere cells in an aqueous environment.
Claim 6
Dependent Claim
16 words
The polypeptide chains of claim 1 or 3 wherein the apolar amino acids comprise alanine residues.
Claim 7
Dependent Claim
18 words
The polypeptide chains of claim 1 or 3 wherein the crosslinkable amino acids comprise tyrosine and lysine residues.
Claim 8
Dependent Claim
12 words
The composition of claim 1 wherein the polypeptide chains are covalently crosslinked.
Claim 9
Dependent Claim
11 words
The polypeptide chains of claim 3 or 6 crosslinked by glutaraldehyde.
Claim 10
Dependent Claim
14 words
The polypeptide of claim 3 or 6 crosslinked by treatment with a tyrosinase enzyme.
Claim 11
Dependent Claim
33 words
A synthetic matrix capable of maintaining a therapeutic compound at a site of application in vivo, said matrix comprising the crosslinked synthetic polypeptide chains of claims 3 and a therapeutic compound dispersed therein.
Claim 12
Dependent Claim
37 words
The synthetic matrix of claim 3 or 9 wherein said polypeptide chains comprise one or more copies of the amino acid sequence of (Seq. ID No. 3): (Ala-Ala-Ala-Lys-Tyr-Lys-Ala-Ala-Ala-Ala-Tyr-Lys-Tyr-Ala).sub.b where b is a number from 1 to 100.
Claim 13
Dependent Claim
21 words
An artificial adhesive matrix for filling tissue gaps, the matrix comprising the crosslinked synthetic polypeptide chains of claims 3 or 9.
Claim 14
Dependent Claim
31 words
A composition for stimulating cell growth comprising the crosslinked synthetic polypeptide chains of claim 3 or 9 and a compound capable of stimulating cell growth dispersed among said crosslinked polypeptide chains.
Claim 15
Dependent Claim
738 words
The composition of claim 12 wherein said compound is a growth factor selected from the group consisting of: EGF, IGF, TGF-α, TGF-β, PDGF, and FGF. __________________________________________________________________________
SEQUENCE LISTING
(1) GENERAL INFORMATION:
(iii) NUMBER OF SEQUENCES: 12
(2) INFORMATION FOR SEQ ID NO:1:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: Peptide
(B) LOCATION: 1..10
(D) OTHER INFORMATION: /note="Pro #osoft Corp
3- hydroxyproline or 4-hydroxyproline and Xaa is
3,4- dihydroxylphenylalanine"
(x) PUBLICATION INFORMATION:
(A) AUTHORS: Waite,, J. H.
Housley, Timothy J.
Tanzer, Marvin L.
(B) TITLE: Peptide Repeats in a Mussel Glue
Protein:Theme and Variations
(C) JOURNAL: Biochemistry
(D) VOLUME: 24
(E) ISSUE: 19
(F) PAGES: 5010-5014
(G) DATE: 1985
(K) RELEVANT RESIDUES IN SEQ ID NO:1: FROM 1 TO 10
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1:
AlaLysProSerTyrProPr oThrXaaLys
1510
(2) INFORMATION FOR SEQ ID NO:2:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 14 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: Protein
(B) LOCATION: 1..14
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:2:
XaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaaXaa
1510
(2) INFORMATION FOR SEQ ID NO:3:
(i ) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 14 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: Protein
(B) LOCATION: 1..14
(D) OTHER INFORMATION: /note="The sequence may be
repeated up to at least about 100 times in a
polypeptide chain"
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:
AlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAla
1510
(2) INFORMATION FOR SEQ ID NO:4:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 21 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:4:
AlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAlaAl aAla
151015
AlaLysTyrLysAla
20
(2) INFORMATION FOR SEQ ID NO:5:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 10 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: Peptide
(B) LOCATION: 1..10
(D) OTHER INFORMATION: /note="Prolines at amino acid
residues 6 and 7 are either 3-hydroxyproline or
4- hydroxyproline"
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:
AlaLysProSerTyrProProThrTyrLys
1510
(2) INFORMATION FOR SEQ ID NO:6:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 18 amino acids
(B) TYPE: amino acid
(C) STRANDEDNESS: single
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: peptide
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:6:
LysGluThrAlaAlaAlaLysPheGluArgGlnHisAsnLeuGluAsp
151015
AlaGly
(2) INFORMATION FOR SEQ ID NO:7:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 63 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: unknown
(ii) MOLECULE TYPE: cDNA
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: CDS
(B ) LOCATION: 3..59
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:7:
CCATGGCTGCTGCAGCTAAGTACAAAGCAGCCGCTGCATATAAATAT47
MetAlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyr
15 1015
GCCGCAGCTGGCTAGC63
AlaAlaAlaGly
(2) INFORMATION FOR SEQ ID NO:8:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 19 amino acids
(B) TYPE: amino acid
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:8:
MetAlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAla
151015
AlaAlaGly
(2) INFORMATION FOR SEQ ID NO:9:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 63 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: unknown
(ii) MOLECULE TYPE: cDNA
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: CDS
(B) LOCATION: 3..59
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:9:
CCATGGCAGCAGCTG CTAAGTACAAAGCAGCCGCTGCATATAAATAT47
MetAlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyr
151015
GCTGCTGCAGGC TAGC63
AlaAlaAlaGly
(2) INFORMATION FOR SEQ ID NO:10:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 19 amino acids
(B) TYPE: amino acid
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:10:
MetAlaAlaAla AlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAla
151015
AlaAlaGly
(2) INFORMATION FOR SEQ ID NO:11:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 105 base pairs
(B) TYPE: nucleic acid
(C) STRANDEDNESS: double
(D) TOPOLOGY: both
(ii) MOLECULE TYPE: cDNA
(iii) HYPOTHETICAL: NO
(iv) ANTI-SENSE: NO
(v) FRAGMENT TYPE: N-terminal
(ix) FEATURE:
(A) NAME/KEY: CDS
(B) LOCATION: 3..101
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:
CCATGGCTGCTGCAGCTAAGTACAAAGCAGCCGCTGCATATAAATAT 47
MetAlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyr
151015
GCCGCAGCTGCTAAGTACAAAGCAGCCGCTGCATATAAATATGC TGCT95
AlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAlaAla
202530
GCAGGCTAGC 105
AlaGly
(2) INFORMATION FOR SEQ ID NO:12:
(i) SEQUENCE CHARACTERISTICS:
(A) LENGTH: 33 amino acids
(B) TYPE: amino acid
(D) TOPOLOGY: linear
(ii) MOLECULE TYPE: protein
(xi) SEQUENCE DESCRIPTION: SEQ ID NO:12:
MetAlaAlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAla
151015
AlaAlaAlaLysTyrLysAlaAlaAlaAlaTyrLysTyrAlaAlaAla
202530
Gly
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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) | 1997-12-19 | 1998-06-20 | 1998-12-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2001-12-19 | 2002-06-20 | 2002-12-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2005-12-19 | 2006-06-20 | 2006-12-20 | $7700.00 | Window Closed / Lapsed |