US5206023A — Method and compositions for the treatment and rep…

Claim 1

Independent Claim 100 words

A method of inducing cartilage formation at a selected site in the cartilage tissue of an animal comprising dressing the site with a composition comprising: a biodegradable matrix or matrix-forming material, a proliferation agent at an appropriate concentration in the matrix or matrix-forming material to stimulate the proliferation of repair cells in the matrix, and a transforming factor associated with a delivery system in the matrix or matrix-forming material and at an appropriate concentration such that upon subsequent delivery of the transforming factor to repair cells in the matrix, the repair cells are transformed into chondrocytes that produce cartilage tissue.

Claim 2

Independent Claim 100 words

A method of inducing cartilage formation at a selected site in the cartilage tissue of an animal comprising dressing the site with a composition comprising: a biodegradable matrix or matrix-forming material, a proliferation agent at an appropriate concentration in the matrix or matrix-forming material to stimulate the proliferation of repair cells in the matrix, and a transforming factor associated with a delivery system in the matrix or matrix-forming material and at an appropriate concentration such that upon subsequent delivery of the transforming factor to repair cells in the matrix, the repair cells are transformed into chondrocytes that produce cartilage tissue.

Claim 3

Dependent Claim 69 words

A method according to claim 1 for inducing cartilage formation at a selected site in the cartilage tissue of an animal comprising dressing the site with a composition comprising: a fibrin matrix formed by adding thrombin to a fibrinogen solution, TGF-β present at a concentration of 2-10 ng/ml of fibrinogen solution, and TGF-β encapsulated in liposomes and present at a concentration of greater than 200 ng/ml of fibrinogen solution.

Claim 4

Independent Claim 72 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells, an effective amount of a chemotactic agent to attract repair cells to the matrix and defect, and an effective amount of a transforming factor associated with a delivery system for subsequent delivery to transform repair cells into chondrocytes.

Claim 5

Independent Claim 72 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells, an effective amount of a chemotactic agent to attract repair cells to the matrix and defect, and an effective amount of a transforming factor associated with a delivery system for subsequent delivery to transform repair cells into chondrocytes.

Claim 6

Independent Claim 87 words

A method for treating defects or lesions at a selected site in cartilage in animals which comprises: filling the defect or lesion with a biodegradable matrix containing an effective amount of a chemotactic agent to attract repair cells to the matrix and defect or lesion and an effective amount of a proliferation agent to stimulate proliferation of repair cells, and delivering a transforming factor into the matrix, approximately 1-2 weeks after filling the defect with the matrix, at a concentration sufficient to transform repair cells into chondrocytes.

Claim 7

Independent Claim 87 words

A method for treating defects or lesions at a selected site in cartilage in animals which comprises: filling the defect or lesion with a biodegradable matrix containing an effective amount of a chemotactic agent to attract repair cells to the matrix and defect or lesion and an effective amount of a proliferation agent to stimulate proliferation of repair cells, and delivering a transforming factor into the matrix, approximately 1-2 weeks after filling the defect with the matrix, at a concentration sufficient to transform repair cells into chondrocytes.

Claim 8

Dependent Claim 33 words

The method according to claim 3 or 4 further comprising the step of covering the surface of the defect with fibrin glue or transglutaminase prior to filling the defect with the biodegradable matrix.

Claim 9

Independent Claim 79 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with an agent to remove proteoglycan from the surface of the defect, removing the agent, and dressing the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells and containing a transforming factor associated with a delivery system that subsequently releases the transforming factor at a concentration sufficient to transform repair cells into chondrocytes.

Claim 10

Independent Claim 79 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with an agent to remove proteoglycan from the surface of the defect, removing the agent, and dressing the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells and containing a transforming factor associated with a delivery system that subsequently releases the transforming factor at a concentration sufficient to transform repair cells into chondrocytes.

Claim 11

Independent Claim 77 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with an agent to remove proteoglycan from the surface of the defect, removing the agent, dressing the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells, and delivering a transforming factor into the matrix approximately 1-2 weeks after filling the defect, at a concentration sufficient to transform repair cells into chondrocytes.

Claim 12

Independent Claim 77 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect with an agent to remove proteoglycan from the surface of the defect, removing the agent, dressing the defect with a biodegradable matrix containing an effective amount of a proliferation agent to stimulate proliferation of repair cells, and delivering a transforming factor into the matrix approximately 1-2 weeks after filling the defect, at a concentration sufficient to transform repair cells into chondrocytes.

Claim 13

Dependent Claim 37 words

The method according to claim 6 or 7 further comprising the step of covering the surface of the defect or lesion with fibrin glue or transglutaminase prior to dressing the defect or lesion with the biodegradable matrix.

Claim 14

Dependent Claim 37 words

The method according to claim 6 or 7 wherein the biodegradable matrix also contains a chemotactic agent at a concentration sufficient to attract repair cells to the matrix and area of the defect or lesion in cartilage.

Claim 15

Dependent Claim 42 words

The method of claim 6 or 7 in which the agent to remove proteoglycan from the surface of the defect is selected from the group consisting of chondroitinase ABC, chondroitinase AC, hyaluronidase, pepsin, papain, trypsin, chymotrypsin, pronase, stromelysin and Staph V8 protease.

Claim 16

Dependent Claim 18 words

The method of claim 9 wherein the proliferation agent, the chemotactic agent, and the transforming factor are TGF-β.

Claim 17

Dependent Claim 40 words

The method of claim 3 or 6 in which the delivery system for the delivery of the transforming factor is selected from the group consisting of liposomes, bioerodible polymers, collagen fibers chemically linked to heparin sulfate proteoglycans, and carbohydrate-based corpuscles.

Claim 18

Dependent Claim 28 words

The method of claim 3, 4, 6 or 7 in which the biodegradable matrix is selected from the group consisting of fibrin, collagen, gelatin, Sepharose or combinations thereof.

Claim 19

Dependent Claim 39 words

The method according to claim 3, 4, 6 or 7 wherein the biodegradable matrix is fibrin which is formed by addition of thrombin to a solution of fibrinogen immediately before filling the defect or lesion with the fibrinogen solution.

Claim 20

Dependent Claim 45 words

The method according to claim 9 wherein the proliferation agent and the chemotactic agent is TGF-β at a concentration of 2-10 ng/ml of matrix, and the transforming factor is TGF-β encapsulated in liposomes and present at a concentration of greater than 200 ng/ml of matrix.

Claim 21

Dependent Claim 43 words

The method according to claim 6 or 7 wherein the agent to remove proteoglycan from the surface of the defect is chondroitinase ABC, and the defect is filled for 4 minutes with a solution comprising chondroitinase ABC at a concentration of 1 unit/ml.

Claim 22

Dependent Claim 25 words

The method according to claim 3, 4, 6 or 7 wherein the biodegradable matrix further contains a cell adhesion promoting factor comprising the tripeptide Arg-Gly-Asp.

Claim 23

Independent Claim 106 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect or lesion area with a sterile solution of chondroitinase ABC at a concentration of 1 unit/ml for 4 minutes, removing the solution of chondroitinase ABC, rinsing the defect area with sterile physiologic saline, drying the defect area, adding 2 units of thrombin to each ml of a matrix-forming solution comprising I mg/ml of fibrinogen, and containing TGF-β a concentration of 2-10 ng/ml, and TGF-β in liposomes for subsequent delivery at a concentration greater than 200 ng/ml, and filling the defect with the matrix-forming solution immediately after addition of the thrombin.

Claim 24

Independent Claim 106 words

A method for treating defects or lesions in cartilage in animals which comprises: filling the defect or lesion area with a sterile solution of chondroitinase ABC at a concentration of 1 unit/ml for 4 minutes, removing the solution of chondroitinase ABC, rinsing the defect area with sterile physiologic saline, drying the defect area, adding 2 units of thrombin to each ml of a matrix-forming solution comprising I mg/ml of fibrinogen, and containing TGF-β a concentration of 2-10 ng/ml, and TGF-β in liposomes for subsequent delivery at a concentration greater than 200 ng/ml, and filling the defect with the matrix-forming solution immediately after addition of the thrombin.

Claim 25

Dependent Claim 31 words

The method according to claim 18 further comprising the step of covering the surface of the defect with fibrin glue or transglutaminase prior to filling the defect with the matrix-forming solution.

Claim 26

Dependent Claim 20 words

The method according to claim 18 wherein the TGF-β in liposomes is at a concentration of greater than 500 ng/ml.

Claim 27

Dependent Claim 36 words

The method according to claim 3, wherein the composition further comprises a chemotactic agent at an appropriate concentration in the matrix or matrix-forming material to attract repair cells to the selected site in the cartilage tissue.

Claim 28

Dependent Claim 18 words

The method according to claim 6 or 7, wherein the cartilage tissue to be treated is meniscal cartilage.

Claim 29

Independent Claim 24 words

The method according to any one of claims 3 or 4, wherein the proliferation agent, the chemotactic agent, and the transforming factor are TGF-β.

Claim 30

Dependent Claim 45 words

The method according to claim 3, wherein the proliferation agent and the chemotactic agent are TGF-β at a concentration of 2-10 ng/ml of matrix, and the transforming factor at TGF-β encapsulated in liposomes and present at a concentration of greater than 200 ng/ml of matrix.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1996-04-26	1996-10-26	1997-04-27	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2000-04-26	2000-10-26	2001-04-27	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2004-04-26	2004-10-26	2005-04-27	$7700.00	Window Closed / Lapsed

Method and compositions for the treatment and repair of defects or lesions in cartilage

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