US6033654A — Bonding together tissue with adhesive containing …

Claim 1

Independent Claim 97 words

A crosslinked protein composition, said protein prior to crosslinking comprising at least 70 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), where in at least two repetitive units an amino acid is substituted with at least one of lysine or arginine, said protein prior to crosslinking having a lysine and arginine equivalent weight in the range of 1 to 20 kD, wherein said protein comprises at least two amino acids comprising a functional group that is capable of reacting with at least one of aldehyde, isocyanate, thioisocyanate and activated carboxy.

Claim 2

Dependent Claim 97 words

A crosslinked protein composition, said protein prior to crosslinking comprising at least 70 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), where in at least two repetitive units an amino acid is substituted with at least one of lysine or arginine, said protein prior to crosslinking having a lysine and arginine equivalent weight in the range of 1 to 20 kD, wherein said protein comprises at least two amino acids comprising a functional group that is capable of reacting with at least one of aldehyde, isocyanate, thioisocyanate and activated carboxy.

Claim 3

Dependent Claim 70 words

A kit comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two amino acids that comprise functional groups capable of reacting with said crosslinking agent.

Claim 4

Dependent Claim 70 words

A kit comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two amino acids that comprise functional groups capable of reacting with said crosslinking agent.

Claim 5

Dependent Claim 16 words

A kit according to claim 2, wherein at least one of said functional groups is amino.

Claim 6

Dependent Claim 35 words

A kit according to claim 2, wherein said functional groups are as a result of reacting a naturally occurring amino acid in said protein polymer with a polyfunctional compound without setting up of said composition.

Claim 7

Dependent Claim 43 words

A kit according to claim 2, wherein said repetitive units further comprise GXX, wherein the X's are the same or different and X is any amino acid, at least 10 number % and not more than 60 number % of X's being proline.

Claim 8

Dependent Claim 28 words

A kit according to claim 2, wherein said crosslinking agent has a plurality of reactive groups selected from the croup consisting of aldehyde, isocyanate, thioisocyanate and activated carboxy.

Claim 9

Dependent Claim 79 words

A kit comprising a protein block copolymer of at least 30 kD comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, said copolymer having a lysine and arginine equivalent weight in the range of 1 to 40 kD, and a crosslinking agent selected from the group consisting of glutaraldehyde and aliphatic diisocyanates.

Claim 10

Dependent Claim 79 words

A kit comprising a protein block copolymer of at least 30 kD comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, said copolymer having a lysine and arginine equivalent weight in the range of 1 to 40 kD, and a crosslinking agent selected from the group consisting of glutaraldehyde and aliphatic diisocyanates.

Claim 11

Independent Claim 119 words

A method of mairtaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two functional groups capable of reacting with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 12

Independent Claim 119 words

A method of mairtaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two functional groups capable of reacting with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 13

Dependent Claim 16 words

A method according to claim 8, wherein at least one of said functional groups is amino.

Claim 14

Dependent Claim 39 words

A method according to claim 8, wherein at least one of said functional groups is as a result of reacting a naturally occurring amino acid in said protein polymer with a polyfunctional compound without setting up of said composition.

Claim 15

Dependent Claim 43 words

A method according to claim 8, wherein said repetitive units further comprise GXX, wherein the X's are the same or different and X is any amino acid, at least 10 number % and not more than 60 number % of X's being proline.

Claim 16

Dependent Claim 23 words

A method according to claim 8, wherein said precursor composition further comprises a difunctional compound capable of reacting with said polyfunctional crosslinking compound.

Claim 17

Dependent Claim 14 words

A method according to claim 12, wherein said difunctional compound is lysine or arginine.

Claim 18

Independent Claim 105 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent reactive with amino groups and a protein block copolymer comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 19

Independent Claim 105 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent reactive with amino groups and a protein block copolymer comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 20

Dependent Claim 27 words

A method according to claim 14, wherein said protein block copolymer has an equivalent weight per lysine and arginine in the range of 1 to 40 kD.

Claim 21

Dependent Claim 38 words

A method according to claim 14, wherein each block of said block copolymer has at least two repetitive units and the ratio of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:1) to Gly-Val-Gly-Val-Pro (SEQ ID NO:2) is in the range of 1:1-16.

Claim 22

Dependent Claim 29 words

A method according to claim 14, wherein said crosslinking agent has a plurality of amino reactive groups selected from the group consisting of aldehyde, isocyanate, thioisocyanate and activated carboxy.

Claim 23

Dependent Claim 12 words

A method according to claim 17, wherein said reactive group is isocyanate.

Claim 24

Dependent Claim 19 words

A method according to claim 14, wherein said precursor composition further comprises at least one of lysine or arginine.

Claim 25

Independent Claim 133 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent selected from the group consisting of glutaraldehyde and polymethylene diisocyanate and a protein block copolymer of at least 30 kD comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, said copolymer having a lysine and arginine equivalent weight in the range of 3 to 15 kD, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 26

Independent Claim 133 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising a polyfunctional crosslinking agent selected from the group consisting of glutaraldehyde and polymethylene diisocyanate and a protein block copolymer of at least 30 kD comprising at least 40 weight % of repetitive units of Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02), wherein at least two amino acids of said protein block copolymer are substituted with lysine or arginine, said copolymer having a lysine and arginine equivalent weight in the range of 3 to 15 kD, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 27

Independent Claim 111 words

A method of sealing a defect in viable tissue, said method comprising: applying to said defect a precursor composition comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two amino acids comprising functional groups capable of reacting with said crosslinking agent, which functional groups react with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; whereby said defect is sealed.

Claim 28

Independent Claim 111 words

A method of sealing a defect in viable tissue, said method comprising: applying to said defect a precursor composition comprising a polyfunctional crosslinking agent and a protein polymer comprising at least 40 weight % of repetitive units, wherein said repetitive units are Gly-Ala-Gly-Ala-Gly-Ser (SEQ ID NO:01) and Gly-Val-Gly-Val-Pro (SEQ ID NO:02) and wherein both of said repetitive units are present to form a block copolymer protein, wherein said protein polymer comprises at least two amino acids comprising functional groups capable of reacting with said crosslinking agent, which functional groups react with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; whereby said defect is sealed.

Claim 29

Dependent Claim 43 words

A method according to claim 21, wherein said repetitive units further comprise CXX, wherein the X's are the same or different and X is any amino acid, at least 10 number % and not more than 60 number % of X's being proline.

Claim 30

Dependent Claim 23 words

A method according to claim 21, wherein said tissue is the wall of a vessel of the cardiovascular system, lung, dura or colon.

Claim 31

Independent Claim 131 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising (1) a polyfunctional crosslinking agent comprising 2-aminoethyl glycinate, cholinyl lysinate or 1,3-propanediyl glycinate reacted with a difunctional compound which reacts with amino groups, and (2) a protein polymer comprising at least 40 weight % of repetitive units of from 3 to 30 amino acids of at least one naturally occurring structural protein, where there are at least two amino functional groups present in said protein polymer, which amino functional groups react with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Claim 32

Independent Claim 131 words

A method of maintaining separated viable tissue in proximate relationship, said method comprising: applying to said separated viable tissue to hold together said tissue when said tissue is in contiguous relationship, a precursor composition comprising (1) a polyfunctional crosslinking agent comprising 2-aminoethyl glycinate, cholinyl lysinate or 1,3-propanediyl glycinate reacted with a difunctional compound which reacts with amino groups, and (2) a protein polymer comprising at least 40 weight % of repetitive units of from 3 to 30 amino acids of at least one naturally occurring structural protein, where there are at least two amino functional groups present in said protein polymer, which amino functional groups react with said crosslinking agent, whereby said precursor composition sets up to a strongly adherent adhesive composition; with said separated viable tissue held in proximate relationship.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2003-03-07	2003-09-06	2004-03-07	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2007-03-07	2007-09-06	2008-03-07	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2011-03-07	2011-09-06	2012-03-07	$7700.00	Window Closed / Lapsed

Bonding together tissue with adhesive containing polyfunctional crosslinking agent and protein polymer

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